TGFA1_MOUSE
ID TGFA1_MOUSE Reviewed; 860 AA.
AC Q3UR70; Q8BKN4;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Transforming growth factor-beta receptor-associated protein 1;
DE Short=TGF-beta receptor-associated protein 1;
DE Short=TRAP-1;
DE Short=TRAP1;
GN Name=Tgfbrap1;
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 [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Osteoclast, and Spinal ganglion;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, 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 [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=20961651; DOI=10.1016/j.imbio.2010.07.006;
RA Messler S., Kropp S., Episkopou V., Felici A., Wurthner J., Lemke R.,
RA Jerabek-Willemsen M., Willecke R., Scheu S., Pfeffer K., Wurthner J.U.;
RT "The TGF-beta signaling modulators TRAP1/TGFBRAP1 and VPS39/Vam6/TLP are
RT essential for early embryonic development.";
RL Immunobiology 216:343-350(2011).
RN [6]
RP INTERACTION WITH RAB5C, AND SUBUNIT.
RX PubMed=25266290; DOI=10.1111/tra.12232;
RA Perini E.D., Schaefer R., Stoeter M., Kalaidzidis Y., Zerial M.;
RT "Mammalian CORVET is required for fusion and conversion of distinct early
RT endosome subpopulations.";
RL Traffic 15:1366-1389(2014).
CC -!- FUNCTION: Plays a role in the TGF-beta/activin signaling pathway. It
CC associates with inactive heteromeric TGF-beta and activin receptor
CC complexes, mainly through the type II receptor, and is released upon
CC activation of signaling. May recruit SMAD4 to the vicinity of the
CC receptor complex and facilitate its interaction with receptor-regulated
CC Smads, such as SMAD2 (By similarity). {ECO:0000250}.
CC -!- FUNCTION: Plays a role in vesicle-mediated protein trafficking of the
CC endocytic membrane transport pathway. Believed to act as a component of
CC the putative CORVET endosomal tethering complexes which is proposed to
CC be involved in the Rab5-to-Rab7 endosome conversion probably
CC implicating MON1A/B, and via binding SNAREs and SNARE complexes to
CC mediate tethering and docking events during SNARE-mediated membrane
CC fusion. The CORVET complex is proposed to function as a Rab5 effector
CC to mediate early endosome fusion probably in specific endosome
CC subpopulations. Functions predominantly in APPL1-containing endosomes
CC and in degradative but not recycling trafficking of endocytosed cargo
CC (By similarity). {ECO:0000250|UniProtKB:Q8WUH2}.
CC -!- SUBUNIT: Interacts with TGFBR2 and ACVR2B; in the absence of ligand
CC stimulation. Interacts with TGFBR1, ACVRL1, BMPR1A and ACVR1B; in the
CC absence of ligand stimulation and to a less extent. Interacts with
CC SMAD4; the interaction seems to be mutually exclusive with the
CC interaction of SMAD4 and phosphorylated SMAD2. May interact with ALOX5
CC (By similarity). Interacts with RAB5C. Interacts with VPS8, VPS11 and
CC VPS16. Component of the putative class C core vacuole/endosome
CC tethering (CORVET) complex; the core of which composed of the class C
CC Vps proteins VPS11, VPS16, VPS18 and VPS33A, is associated with VPS8
CC and TGFBRAP1 (PubMed:25266290). {ECO:0000250|UniProtKB:Q8WUH2,
CC ECO:0000269|PubMed:25266290, ECO:0000305|PubMed:25266290}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Early endosome
CC {ECO:0000250|UniProtKB:Q8WUH2}. Note=Colocalizes with TGF-beta
CC receptors in the absence of signaling. {ECO:0000250|UniProtKB:Q8WUH2}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UR70-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UR70-2; Sequence=VSP_034944, VSP_034945;
CC -!- DISRUPTION PHENOTYPE: Embryonic lethal, both before blastula stage or
CC during gastrulation. {ECO:0000269|PubMed:20961651}.
CC -!- SIMILARITY: Belongs to the TRAP1 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK051333; BAC34606.1; -; mRNA.
DR EMBL; AK141742; BAE24818.1; -; mRNA.
DR EMBL; AK159332; BAE34997.1; -; mRNA.
DR EMBL; CH466589; EDK96916.1; -; Genomic_DNA.
DR EMBL; BC138866; AAI38867.1; -; mRNA.
DR EMBL; BC138867; AAI38868.1; -; mRNA.
DR CCDS; CCDS14920.1; -. [Q3UR70-1]
DR RefSeq; NP_001013043.1; NM_001013025.2. [Q3UR70-1]
DR RefSeq; XP_006496364.1; XM_006496301.3.
DR RefSeq; XP_006496365.1; XM_006496302.3. [Q3UR70-1]
DR RefSeq; XP_006496366.1; XM_006496303.2. [Q3UR70-1]
DR AlphaFoldDB; Q3UR70; -.
DR BioGRID; 215781; 10.
DR IntAct; Q3UR70; 1.
DR STRING; 10090.ENSMUSP00000092624; -.
DR iPTMnet; Q3UR70; -.
DR PhosphoSitePlus; Q3UR70; -.
DR EPD; Q3UR70; -.
DR MaxQB; Q3UR70; -.
DR PaxDb; Q3UR70; -.
DR PeptideAtlas; Q3UR70; -.
DR PRIDE; Q3UR70; -.
DR ProteomicsDB; 263037; -. [Q3UR70-1]
DR ProteomicsDB; 263038; -. [Q3UR70-2]
DR Antibodypedia; 49233; 158 antibodies from 22 providers.
DR DNASU; 73122; -.
DR Ensembl; ENSMUST00000095014; ENSMUSP00000092624; ENSMUSG00000070939. [Q3UR70-1]
DR Ensembl; ENSMUST00000186694; ENSMUSP00000140132; ENSMUSG00000070939. [Q3UR70-1]
DR GeneID; 73122; -.
DR KEGG; mmu:73122; -.
DR UCSC; uc007ave.1; mouse. [Q3UR70-1]
DR UCSC; uc007avh.1; mouse. [Q3UR70-2]
DR CTD; 9392; -.
DR MGI; MGI:2447427; Tgfbrap1.
DR VEuPathDB; HostDB:ENSMUSG00000070939; -.
DR eggNOG; KOG2063; Eukaryota.
DR GeneTree; ENSGT00530000063596; -.
DR HOGENOM; CLU_004190_3_0_1; -.
DR InParanoid; Q3UR70; -.
DR OMA; DKKLCQV; -.
DR OrthoDB; 682722at2759; -.
DR PhylomeDB; Q3UR70; -.
DR TreeFam; TF328650; -.
DR BioGRID-ORCS; 73122; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Tgfbrap1; mouse.
DR PRO; PR:Q3UR70; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q3UR70; protein.
DR Bgee; ENSMUSG00000070939; Expressed in secondary oocyte and 218 other tissues.
DR ExpressionAtlas; Q3UR70; baseline and differential.
DR Genevisible; Q3UR70; MM.
DR GO; GO:0033263; C:CORVET complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0046332; F:SMAD binding; ISO:MGI.
DR GO; GO:0005160; F:transforming growth factor beta receptor binding; ISO:MGI.
DR GO; GO:0006914; P:autophagy; IBA:GO_Central.
DR GO; GO:0034058; P:endosomal vesicle fusion; ISO:MGI.
DR GO; GO:0008333; P:endosome to lysosome transport; ISO:MGI.
DR GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; ISO:MGI.
DR InterPro; IPR000547; Clathrin_H-chain/VPS_repeat.
DR InterPro; IPR001180; CNH_dom.
DR InterPro; IPR032914; Vam6/VPS39/TRAP1.
DR InterPro; IPR019452; VPS39/TGF_beta_rcpt-assoc_1.
DR InterPro; IPR019453; VPS39/TGF_beta_rcpt-assoc_2.
DR PANTHER; PTHR12894; PTHR12894; 1.
DR Pfam; PF00637; Clathrin; 1.
DR Pfam; PF00780; CNH; 1.
DR Pfam; PF10366; Vps39_1; 1.
DR Pfam; PF10367; Vps39_2; 1.
DR PROSITE; PS50236; CHCR; 1.
DR PROSITE; PS50219; CNH; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Endosome; Protein transport;
KW Reference proteome; Transport.
FT CHAIN 1..860
FT /note="Transforming growth factor-beta receptor-associated
FT protein 1"
FT /id="PRO_0000345406"
FT DOMAIN 24..297
FT /note="CNH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT REPEAT 564..732
FT /note="CHCR"
FT VAR_SEQ 231..247
FT /note="MFATVAGISQRAPVHWS -> EEGWGSLLMAPASCLLS (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_034944"
FT VAR_SEQ 248..860
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_034945"
SQ SEQUENCE 860 AA; 97303 MW; B86BD77735D04C7B CRC64;
MMNIKAFTLV SAVERELLMG DRDHISIECV ECCGRNLYVG TNDCFIYHFL LEEKAMPTGT
ATFVATKQLH RHLGFKKPVN ELCAASALNR LLVLCDNSIT LVNMLNLEPV PSGARIKGAT
TFAVNESPVN GDPFCVEVCI ISVKRRTVQM FLVYEDRVQI VKEVSTPEQP LAVAVDGYFL
CLALTTQYII LNYSTGLSQD LFPYCSEEKP PIVKRIGRQE FLLAGPGGLG MFATVAGISQ
RAPVHWSENV IGAAVCFPYV IALDDEFITV HSMLDQQQKQ TLPFKEGHIL QDFEGRVIVA
TSKGVYILVP LPLEKQIQDL LANRRVEEAL VLAKGARRNI PKEKFQVMYR RILQQAGFIQ
FAQLQFLEAK ELFRSSQLDV RELISLYPFL LPTSSSFTRS HPPLHEYADL NQLTQGDQEK
MAKCKRFLMS YLNEIRSTEV ANGYKEDIDT ALLKLYAEAD HDSLLDLLVT ENFCLLTDSA
AWLEKHKKYF ALGLLYHYNK QDASAVQLWV NIVNGDIQDS TRSDLYEYIV DFLTYCLDQE
LVWTHADWLL QKSEEIGVQI FTKRPLDEQQ QTSFNPDNII SSLKKYPKAL VKYLEHLVID
RRLQKEEYHT HLAILYLEEV LRQRVSTGGK DVEATETQAK LRRLLQKSDL YRVHLLKEKV
QGAGLPMESA ILHGKLGEHE KALHILVHEM GDFSAAEDYC LWSSEGQGAA CRQRLFHTLL
AMYLRAGPSA QDLTVAAVDL LNHHAREFDV TQVLQLLPDT WSVQLLCPFL MGAMRDSIHA
RRTTQVALGL AKSENLIYMY DKMKLKGNAV RLSERELCQL CQNPFGEPVF VRYPNGGLVH
THCAASRHTA PSSPSPGTRT
