ID   TGFA1_HUMAN             Reviewed;         860 AA.
AC   Q8WUH2; A8K5R7; D3DVJ8; O60466;
DT   22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2002, sequence version 1.
DT   27-MAR-2024, entry version 145.
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   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], FUNCTION, INTERACTION WITH TGFBR1, AND VARIANT
RP   ARG-725.
RX   PubMed=9545258; DOI=10.1074/jbc.273.16.9365;
RA   Charng M.-J., Zhang D., Kinnunen P., Schneider M.D.;
RT   "A novel protein distinguishes between quiescent and activated forms of the
RT   type I transforming growth factor beta receptor.";
RL   J. Biol. Chem. 273:9365-9368(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-725.
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lymph;
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   [6]
RP   INTERACTION WITH ALOX5.
RX   PubMed=10051563; DOI=10.1073/pnas.96.5.1881;
RA   Provost P., Samuelsson B., Radmark O.;
RT   "Interaction of 5-lipoxygenase with cellular proteins.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:1881-1885(1999).
RN   [7]
RP   FUNCTION, INTERACTION WITH TGFBR2; ACVR2B; TGFBR1; ACVRL1; BMPR1A; ACVR1B
RP   AND SMAD4, AND SUBCELLULAR LOCATION.
RX   PubMed=11278302; DOI=10.1074/jbc.m006473200;
RA   Wurthner J.U., Frank D.B., Felici A., Green H.M., Cao Z., Schneider M.D.,
RA   McNally J.G., Lechleider R.J., Roberts A.B.;
RT   "Transforming growth factor-beta receptor-associated protein 1 is a Smad4
RT   chaperone.";
RL   J. Biol. Chem. 276:19495-19502(2001).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [9]
RP   FUNCTION, FUNCTION OF THE CORVET COMPLEX, INTERACTION WITH VPS8; VPS11 AND
RP   VPS16, SUBUNIT, AND SUBCELLULAR LOCATION.
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. {ECO:0000269|PubMed:11278302,
CC       ECO:0000269|PubMed:9545258}.
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 (PubMed:25266290). Functions predominantly in APPL1-
CC       containing endosomes and in degradative but not recycling trafficking
CC       of endocytosed cargo (PubMed:25266290). {ECO:0000269|PubMed:25266290,
CC       ECO:0000305|PubMed:25266290}.
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 (PubMed:9545258,
CC       PubMed:11278302). May interact with ALOX5 (PubMed:10051563). Interacts
CC       with RAB5C (By similarity). Interacts with VPS8, VPS11 and VPS16.
CC       Component of the putative class C core vacuole/endosome tethering
CC       (CORVET) complex; the core of which composed of the class C Vps
CC       proteins VPS11, VPS16, VPS18 and VPS33A, is associated with VPS8 and
CC       TGFBRAP1 (PubMed:25266290). {ECO:0000250|UniProtKB:Q3UR70,
CC       ECO:0000269|PubMed:10051563, ECO:0000269|PubMed:11278302,
CC       ECO:0000269|PubMed:25266290, ECO:0000269|PubMed:9545258,
CC       ECO:0000305|PubMed:25266290}.
CC   -!- INTERACTION:
CC       Q8WUH2; Q9H270: VPS11; NbExp=3; IntAct=EBI-2954829, EBI-373380;
CC       Q8WUH2; Q9H269: VPS16; NbExp=3; IntAct=EBI-2954829, EBI-2655929;
CC       Q8WUH2; Q8N3P4: VPS8; NbExp=2; IntAct=EBI-2954829, EBI-7261494;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11278302}. Early
CC       endosome {ECO:0000269|PubMed:25266290}. Note=Colocalizes with TGF-beta
CC       receptors in the absence of signaling.
CC   -!- SIMILARITY: Belongs to the TRAP1 family. {ECO:0000305}.
CC   -!- CAUTION: In (PubMed:9545258) and in (PubMed:10051563) experimental
CC       information is given for a truncated version of TGFBRAP1 (sequence of
CC       474-860), which was later shown to act as a dominant negative.
CC       {ECO:0000305|PubMed:10051563, ECO:0000305|PubMed:9545258}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="https://atlasgeneticsoncology.org/gene/42542/TGFBRAP1";
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DR   EMBL; AF022795; AAC16903.1; -; mRNA.
DR   EMBL; AK291382; BAF84071.1; -; mRNA.
DR   EMBL; AC012360; AAY15010.1; -; Genomic_DNA.
DR   EMBL; CH471127; EAX01764.1; -; Genomic_DNA.
DR   EMBL; CH471127; EAX01765.1; -; Genomic_DNA.
DR   EMBL; BC020548; AAH20548.1; -; mRNA.
DR   CCDS; CCDS2067.1; -.
DR   PIR; T08622; T08622.
DR   RefSeq; NP_001136093.1; NM_001142621.2.
DR   RefSeq; NP_004248.2; NM_004257.5.
DR   AlphaFoldDB; Q8WUH2; -.
DR   SMR; Q8WUH2; -.
DR   BioGRID; 114792; 53.
DR   ComplexPortal; CPX-6213; CORVET tethering complex.
DR   CORUM; Q8WUH2; -.
DR   IntAct; Q8WUH2; 18.
DR   STRING; 9606.ENSP00000377027; -.
DR   iPTMnet; Q8WUH2; -.
DR   PhosphoSitePlus; Q8WUH2; -.
DR   BioMuta; TGFBRAP1; -.
DR   DMDM; 74730711; -.
DR   EPD; Q8WUH2; -.
DR   jPOST; Q8WUH2; -.
DR   MassIVE; Q8WUH2; -.
DR   MaxQB; Q8WUH2; -.
DR   PaxDb; 9606-ENSP00000377027; -.
DR   PeptideAtlas; Q8WUH2; -.
DR   ProteomicsDB; 74676; -.
DR   Pumba; Q8WUH2; -.
DR   Antibodypedia; 49233; 163 antibodies from 22 providers.
DR   DNASU; 9392; -.
DR   Ensembl; ENST00000393359.7; ENSP00000377027.2; ENSG00000135966.14.
DR   Ensembl; ENST00000595531.5; ENSP00000471434.2; ENSG00000135966.14.
DR   GeneID; 9392; -.
DR   KEGG; hsa:9392; -.
DR   MANE-Select; ENST00000393359.7; ENSP00000377027.2; NM_004257.6; NP_004248.2.
DR   UCSC; uc002tcq.5; human.
DR   AGR; HGNC:16836; -.
DR   CTD; 9392; -.
DR   DisGeNET; 9392; -.
DR   GeneCards; TGFBRAP1; -.
DR   HGNC; HGNC:16836; TGFBRAP1.
DR   HPA; ENSG00000135966; Low tissue specificity.
DR   MIM; 606237; gene.
DR   neXtProt; NX_Q8WUH2; -.
DR   OpenTargets; ENSG00000135966; -.
DR   PharmGKB; PA134963946; -.
DR   VEuPathDB; HostDB:ENSG00000135966; -.
DR   eggNOG; KOG2063; Eukaryota.
DR   GeneTree; ENSGT00530000063596; -.
DR   HOGENOM; CLU_004190_3_0_1; -.
DR   InParanoid; Q8WUH2; -.
DR   OMA; VLKEIQC; -.
DR   OrthoDB; 198927at2759; -.
DR   PhylomeDB; Q8WUH2; -.
DR   TreeFam; TF328650; -.
DR   PathwayCommons; Q8WUH2; -.
DR   SignaLink; Q8WUH2; -.
DR   SIGNOR; Q8WUH2; -.
DR   BioGRID-ORCS; 9392; 72 hits in 1157 CRISPR screens.
DR   ChiTaRS; TGFBRAP1; human.
DR   GenomeRNAi; 9392; -.
DR   Pharos; Q8WUH2; Tbio.
DR   PRO; PR:Q8WUH2; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q8WUH2; Protein.
DR   Bgee; ENSG00000135966; Expressed in secondary oocyte and 173 other cell types or tissues.
DR   GO; GO:0033263; C:CORVET complex; NAS:ComplexPortal.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR   GO; GO:0046332; F:SMAD binding; IDA:UniProtKB.
DR   GO; GO:0005160; F:transforming growth factor beta receptor binding; IDA:UniProtKB.
DR   GO; GO:0006914; P:autophagy; IBA:GO_Central.
DR   GO; GO:0034058; P:endosomal vesicle fusion; IMP:UniProtKB.
DR   GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB.
DR   GO; GO:0006886; P:intracellular protein transport; IEA:InterPro.
DR   GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB.
DR   GO; GO:0035542; P:regulation of SNARE complex assembly; NAS:ComplexPortal.
DR   GO; GO:0007165; P:signal transduction; IDA:UniProtKB.
DR   GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:UniProtKB.
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; CNH DOMAIN CONTAINING; 1.
DR   PANTHER; PTHR12894:SF27; TRANSFORMING GROWTH FACTOR-BETA RECEPTOR-ASSOCIATED PROTEIN 1; 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.
DR   Genevisible; Q8WUH2; HS.
PE   1: Evidence at protein level;
KW   Cytoplasm; Endosome; Protein transport; Reference proteome; Transport.
FT   CHAIN           1..860
FT                   /note="Transforming growth factor-beta receptor-associated
FT                   protein 1"
FT                   /id="PRO_0000345405"
FT   DOMAIN          24..297
FT                   /note="CNH"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00795"
FT   REPEAT          564..728
FT                   /note="CHCR"
FT   VARIANT         725
FT                   /note="H -> R (in dbSNP:rs2241797)"
FT                   /evidence="ECO:0000269|PubMed:9545258, ECO:0000269|Ref.4"
FT                   /id="VAR_045822"
FT   CONFLICT        805
FT                   /note="L -> S (in Ref. 2; BAF84071)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   860 AA;  97158 MW;  ABDD23BEDC5F4A55 CRC64;
     MMSIKAFTLV SAVERELLMG DKERVNIECV ECCGRDLYVG TNDCFVYHFL LEERPVPAGP
     ATFTATKQLQ RHLGFKKPVN ELRAASALNR LLVLCDNSIS LVNMLNLEPV PSGARIKGAA
     TFALNENPVS GDPFCVEVCI ISVKRRTIQM FLVYEDRVQI VKEVSTAEQP LAVAVDGHFL
     CLALTTQYII HNYSTGVSQD LFPYCSEERP PIVKRIGRQE FLLAGPGGLG MFATVAGISQ
     RAPVHWSENV IGAAVSFPYV IALDDEFITV HSMLDQQQKQ TLPFKEGHIL QDFEGRVIVA
     TSKGVYILVP LPLEKQIQDL LASRRVEEAL VLAKGARRNI PKEKFQVMYR RILQQAGFIQ
     FAQLQFLEAK ELFRSGQLDV RELISLYPFL LPTSSSFTRS HPPLHEYADL NQLTQGDQEK
     MAKCKRFLMS YLNEVRSTEV ANGYKEDIDT ALLKLYAEAD HDSLLDLLVT ENFCLLTDSA
     AWLEKHKKYF ALGLLYHYNN QDAAAVQLWV NIVNGDVQDS TRSDLYEYIV DFLTYCLDEE
     LVWAYADWVL QKSEEVGVQV FTKRPLDEQQ KNSFNPDDII NCLKKYPKAL VKYLEHLVID
     KRLQKEEYHT HLAVLYLEEV LLQRASASGK GAEATETQAK LRRLLQKSDL YRVHFLLERL
     QGAGLPMESA ILHGKLGEHE KALHILVHEL QDFAAAEDYC LWCSEGRDPP HRQQLFHTLL
     AIYLHAGPTA HELAVAAVDL LNRHATEFDA AQVLQMLPDT WSVQLLCPFL MGAMRDSIHA
     RRTMQVALGL ARSENLIYTY DKMKLKGSSI QLSDKKLCQI CQNPFCEPVF VRYPNGGLVH
     THCAASRHTN PSSSSPGTRT
//