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Protein

Transforming growth factor-beta receptor-associated protein 1

Gene

TGFBRAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Plays a role in the TGF-beta/activin signaling pathway. It associates with inactive heteromeric TGF-beta and activin receptor complexes, mainly through the type II receptor, and is released upon activation of signaling. May recruit SMAD4 to the vicinity of the receptor complex and facilitate its interaction with receptor-regulated Smads, such as SMAD2.2 Publications
Plays a role in vesicle-mediated protein trafficking of the endocytic membrane transport pathway. Believed to act as a component of the putative CORVET endosomal tethering complexes which is proposed to be involved in the Rab5-to-Rab7 endosome conversion probably implicating MON1A/B, and via binding SNAREs and SNARE complexes to mediate tethering and docking events during SNARE-mediated membrane fusion. The CORVET complex is proposed to function as a Rab5 effector to mediate early endosome fusion probably in specific endosome subpopulations (PubMed:25266290). Functions predominantly in APPL1-containing endosomes and in degradative but not recycling trafficking of endocytosed cargo (PubMed:25266290).1 Publication1 Publication

Caution

In (PubMed:9545258) and in (PubMed:10051563) experimental information is given for a truncated version of TGFBRAP1 (sequence of 474-860), which was later shown to act as a dominant negative.2 Publications

GO - Molecular functioni

  • SMAD binding Source: UniProtKB
  • transforming growth factor beta receptor binding Source: UniProtKB

GO - Biological processi

  • endosomal vesicle fusion Source: UniProtKB
  • endosome to lysosome transport Source: UniProtKB
  • intracellular protein transport Source: InterPro
  • regulation of transcription, DNA-templated Source: UniProtKB
  • signal transduction Source: UniProtKB
  • transforming growth factor beta receptor signaling pathway Source: UniProtKB

Keywordsi

Biological processProtein transport, Transport

Enzyme and pathway databases

SignaLinkiQ8WUH2

Names & Taxonomyi

Protein namesi
Recommended name:
Transforming growth factor-beta receptor-associated protein 1
Short name:
TGF-beta receptor-associated protein 1
Short name:
TRAP-1
Short name:
TRAP1
Gene namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000135966.12
HGNCiHGNC:16836 TGFBRAP1
MIMi606237 gene
neXtProtiNX_Q8WUH2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome

Pathology & Biotechi

Organism-specific databases

DisGeNETi9392
OpenTargetsiENSG00000135966
PharmGKBiPA134963946

Polymorphism and mutation databases

BioMutaiTGFBRAP1
DMDMi74730711

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003454051 – 860Transforming growth factor-beta receptor-associated protein 1Add BLAST860

Proteomic databases

EPDiQ8WUH2
MaxQBiQ8WUH2
PaxDbiQ8WUH2
PeptideAtlasiQ8WUH2
PRIDEiQ8WUH2
ProteomicsDBi74676

PTM databases

iPTMnetiQ8WUH2
PhosphoSitePlusiQ8WUH2

Expressioni

Gene expression databases

BgeeiENSG00000135966
CleanExiHS_TGFBRAP1
GenevisibleiQ8WUH2 HS

Organism-specific databases

HPAiHPA037672
HPA038397

Interactioni

Subunit structurei

Interacts with TGFBR2 and ACVR2B; in the absence of ligand stimulation. Interacts with TGFBR1, ACVRL1, BMPR1A and ACVR1B; in the absence of ligand stimulation and to a less extent. Interacts with SMAD4; the interaction seems to be mutually exclusive with the interaction of SMAD4 and phosphorylated SMAD2 (PubMed:9545258, PubMed:11278302). May interact with ALOX5 (PubMed:10051563). Interacts with RAB5C (By similarity). Interacts with VPS8, VPS11 and VPS16. Component of the putative class C core vacuole/endosome tethering (CORVET) complex; the core of which composed of the class C Vps proteins VPS11, VPS16, VPS18 and VPS33A, is associated with VPS8 and TGFBRAP1 (PubMed:25266290).By similarity1 Publication4 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • SMAD binding Source: UniProtKB
  • transforming growth factor beta receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114792, 30 interactors
CORUMiQ8WUH2
IntActiQ8WUH2, 10 interactors
STRINGi9606.ENSP00000258449

Structurei

3D structure databases

ProteinModelPortaliQ8WUH2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini24 – 297CNHPROSITE-ProRule annotationAdd BLAST274
Repeati564 – 728CHCRAdd BLAST165

Sequence similaritiesi

Belongs to the TRAP1 family.Curated

Phylogenomic databases

eggNOGiKOG2063 Eukaryota
ENOG410XNSX LUCA
GeneTreeiENSGT00530000063596
HOGENOMiHOG000007291
HOVERGENiHBG108563
InParanoidiQ8WUH2
KOiK20177
OMAiLGMFATV
OrthoDBiEOG091G034A
PhylomeDBiQ8WUH2
TreeFamiTF328650

Family and domain databases

InterProiView protein in InterPro
IPR000547 Clathrin_H-chain/VPS_repeat
IPR001180 CNH_dom
IPR032914 Vam6/VPS39/TRAP1
IPR019452 VPS39/TGF_beta_rcpt-assoc_1
IPR019453 VPS39/TGF_beta_rcpt-assoc_2
PANTHERiPTHR12894 PTHR12894, 1 hit
PfamiView protein in Pfam
PF00637 Clathrin, 1 hit
PF00780 CNH, 1 hit
PF10366 Vps39_1, 1 hit
PF10367 Vps39_2, 1 hit
PROSITEiView protein in PROSITE
PS50236 CHCR, 1 hit
PS50219 CNH, 1 hit

Sequencei

Sequence statusi: Complete.

Q8WUH2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMSIKAFTLV SAVERELLMG DKERVNIECV ECCGRDLYVG TNDCFVYHFL
60 70 80 90 100
LEERPVPAGP ATFTATKQLQ RHLGFKKPVN ELRAASALNR LLVLCDNSIS
110 120 130 140 150
LVNMLNLEPV PSGARIKGAA TFALNENPVS GDPFCVEVCI ISVKRRTIQM
160 170 180 190 200
FLVYEDRVQI VKEVSTAEQP LAVAVDGHFL CLALTTQYII HNYSTGVSQD
210 220 230 240 250
LFPYCSEERP PIVKRIGRQE FLLAGPGGLG MFATVAGISQ RAPVHWSENV
260 270 280 290 300
IGAAVSFPYV IALDDEFITV HSMLDQQQKQ TLPFKEGHIL QDFEGRVIVA
310 320 330 340 350
TSKGVYILVP LPLEKQIQDL LASRRVEEAL VLAKGARRNI PKEKFQVMYR
360 370 380 390 400
RILQQAGFIQ FAQLQFLEAK ELFRSGQLDV RELISLYPFL LPTSSSFTRS
410 420 430 440 450
HPPLHEYADL NQLTQGDQEK MAKCKRFLMS YLNEVRSTEV ANGYKEDIDT
460 470 480 490 500
ALLKLYAEAD HDSLLDLLVT ENFCLLTDSA AWLEKHKKYF ALGLLYHYNN
510 520 530 540 550
QDAAAVQLWV NIVNGDVQDS TRSDLYEYIV DFLTYCLDEE LVWAYADWVL
560 570 580 590 600
QKSEEVGVQV FTKRPLDEQQ KNSFNPDDII NCLKKYPKAL VKYLEHLVID
610 620 630 640 650
KRLQKEEYHT HLAVLYLEEV LLQRASASGK GAEATETQAK LRRLLQKSDL
660 670 680 690 700
YRVHFLLERL QGAGLPMESA ILHGKLGEHE KALHILVHEL QDFAAAEDYC
710 720 730 740 750
LWCSEGRDPP HRQQLFHTLL AIYLHAGPTA HELAVAAVDL LNRHATEFDA
760 770 780 790 800
AQVLQMLPDT WSVQLLCPFL MGAMRDSIHA RRTMQVALGL ARSENLIYTY
810 820 830 840 850
DKMKLKGSSI QLSDKKLCQI CQNPFCEPVF VRYPNGGLVH THCAASRHTN
860
PSSSSPGTRT
Length:860
Mass (Da):97,158
Last modified:March 1, 2002 - v1
Checksum:iABDD23BEDC5F4A55
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti805L → S in BAF84071 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_045822725H → R2 PublicationsCorresponds to variant dbSNP:rs2241797Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF022795 mRNA Translation: AAC16903.1
AK291382 mRNA Translation: BAF84071.1
AC012360 Genomic DNA Translation: AAY15010.1
CH471127 Genomic DNA Translation: EAX01764.1
CH471127 Genomic DNA Translation: EAX01765.1
BC020548 mRNA Translation: AAH20548.1
CCDSiCCDS2067.1
PIRiT08622
RefSeqiNP_001136093.1, NM_001142621.2
NP_004248.2, NM_004257.5
UniGeneiHs.446350
Hs.592796

Genome annotation databases

EnsembliENST00000258449; ENSP00000258449; ENSG00000135966
ENST00000393359; ENSP00000377027; ENSG00000135966
ENST00000595531; ENSP00000471434; ENSG00000135966
GeneIDi9392
KEGGihsa:9392
UCSCiuc002tcq.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTGFA1_HUMAN
AccessioniPrimary (citable) accession number: Q8WUH2
Secondary accession number(s): A8K5R7, D3DVJ8, O60466
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 22, 2008
Last sequence update: March 1, 2002
Last modified: July 18, 2018
This is version 115 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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