TGFA1_HUMAN
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 03-AUG-2022, entry version 136.
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="http://atlasgeneticsoncology.org/Genes/TGFBRAP1ID42542ch2q12.html";
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; 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 BioGRID; 114792; 49.
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; Q8WUH2; -.
DR PeptideAtlas; Q8WUH2; -.
DR PRIDE; Q8WUH2; -.
DR ProteomicsDB; 74676; -.
DR Antibodypedia; 49233; 158 antibodies from 22 providers.
DR DNASU; 9392; -.
DR Ensembl; ENST00000258449.2; ENSP00000258449.1; ENSG00000135966.13.
DR Ensembl; ENST00000393359.7; ENSP00000377027.2; ENSG00000135966.13.
DR Ensembl; ENST00000595531.5; ENSP00000471434.2; ENSG00000135966.13.
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 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; DKKLCQV; -.
DR OrthoDB; 682722at2759; -.
DR PhylomeDB; Q8WUH2; -.
DR TreeFam; TF328650; -.
DR PathwayCommons; Q8WUH2; -.
DR SignaLink; Q8WUH2; -.
DR BioGRID-ORCS; 9392; 71 hits in 1081 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 171 other tissues.
DR Genevisible; Q8WUH2; HS.
DR GO; GO:0033263; C:CORVET complex; IC: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:0035542; P:regulation of SNARE complex assembly; IC:ComplexPortal.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
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; 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 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
