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Protein

Protein TMEPAI

Gene

PMEPA1

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

Functioni

Functions as a negative regulator of TGF-beta signaling and thereby probably plays a role in cell proliferation, differentiation, apoptosis, motility, extracellular matrix production and immunosuppression. In the canonical TGF-beta pathway, ZFYVE9/SARA recruits the intracellular signal transducer and transcriptional modulators SMAD2 and SMAD3 to the TGF-beta receptor. Phosphorylated by the receptor, SMAD2 and SMAD3 then form a heteromeric complex with SMAD4 that translocates to the nucleus to regulate transcription. Through interaction with SMAD2 and SMAD3, LDLRAD4 may compete with ZFYVE9 and SMAD4 and prevent propagation of the intracellular signal (PubMed:20129061, PubMed:24627487). Also involved in down-regulation of the androgen receptor (AR), enhancing ubiquitination and proteasome-mediated degradation of AR, probably by recruiting NEDD4 (PubMed:18703514).3 Publications

GO - Molecular functioni

  • R-SMAD binding Source: UniProtKB
  • WW domain binding Source: UniProtKB

GO - Biological processi

  • androgen receptor signaling pathway Source: UniProtKB
  • negative regulation of pathway-restricted SMAD protein phosphorylation Source: UniProtKB
  • negative regulation of SMAD protein complex assembly Source: UniProtKB
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB

Keywordsi

Molecular functionSignal transduction inhibitor
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-2173788 Downregulation of TGF-beta receptor signaling

Names & Taxonomyi

Protein namesi
Recommended name:
Protein TMEPAI
Alternative name(s):
Prostate transmembrane protein androgen induced 1
Solid tumor-associated 1 protein
Transmembrane prostate androgen-induced protein
Gene namesi
Name:PMEPA1
Synonyms:STAG1, TMEPAI
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi

Organism-specific databases

EuPathDBiHostDB:ENSG00000124225.15
HGNCiHGNC:14107 PMEPA1
MIMi606564 gene
neXtProtiNX_Q969W9

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 40LumenalSequence analysisAdd BLAST40
Transmembranei41 – 63HelicalSequence analysisAdd BLAST23
Topological domaini64 – 287CytoplasmicSequence analysisAdd BLAST224

Keywords - Cellular componenti

Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi161Y → A: Impairs interaction with NEDD4. Impairs polyubiquitination of AR; when associated with A-232. 2 Publications1
Mutagenesisi232Y → A: Impairs interaction with NEDD4. Impairs polyubiquitination of AR; when associated with A-232. 2 Publications1

Organism-specific databases

DisGeNETi56937
OpenTargetsiENSG00000124225
PharmGKBiPA162399822

Polymorphism and mutation databases

BioMutaiPMEPA1
DMDMi20140695

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001854421 – 287Protein TMEPAIAdd BLAST287

Proteomic databases

PaxDbiQ969W9
PeptideAtlasiQ969W9
PRIDEiQ969W9

PTM databases

iPTMnetiQ969W9
PhosphoSitePlusiQ969W9

Expressioni

Tissue specificityi

Highest expression in prostate. Also expressed in ovary.

Inductioni

Up-regulated by androgen and TGF-beta (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000124225
CleanExiHS_PMEPA1
HS_STAG1
ExpressionAtlasiQ969W9 baseline and differential
GenevisibleiQ969W9 HS

Organism-specific databases

HPAiHPA072291

Interactioni

Subunit structurei

Interacts with NEDD4 (via PPxY motifs). Interacts with AR. Interacts with LDLRAD4. Interacts (via the SMAD interaction motif) with SMAD2 and SMAD3.4 Publications

GO - Molecular functioni

  • R-SMAD binding Source: UniProtKB
  • WW domain binding Source: UniProtKB

Protein-protein interaction databases

BioGridi121262, 10 interactors
IntActiQ969W9, 3 interactors
MINTiQ969W9
STRINGi9606.ENSP00000345826

Structurei

3D structure databases

ProteinModelPortaliQ969W9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi158 – 161PPxY motif 14
Motifi186 – 189SMAD interaction motif (SIM)4
Motifi229 – 232PPxY motif 24

Domaini

The PPxY motifs mediate interaction with NEDD4.1 Publication
The SMAD interaction motif is required for interaction with SMAD2 and SMAD3 and the negative regulation of TGF-beta signaling.1 Publication

Sequence similaritiesi

Belongs to the PMEPA1 family.Curated

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IEW4 Eukaryota
ENOG4111QDT LUCA
GeneTreeiENSGT00390000000724
HOGENOMiHOG000276535
HOVERGENiHBG059833
InParanoidiQ969W9
OMAiQRDRFHR
OrthoDBiEOG091G0HDA
PhylomeDBiQ969W9
TreeFamiTF331681

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q969W9-1) [UniParc]FASTAAdd to basket
Also known as: a

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MHRLMGVNST AAAAAGQPNV SCTCNCKRSL FQSMEITELE FVQIIIIVVV
60 70 80 90 100
MMVMVVVITC LLSHYKLSAR SFISRHSQGR RREDALSSEG CLWPSESTVS
110 120 130 140 150
GNGIPEPQVY APPRPTDRLA VPPFAQRERF HRFQPTYPYL QHEIDLPPTI
160 170 180 190 200
SLSDGEEPPP YQGPCTLQLR DPEQQLELNR ESVRAPPNRT IFDSDLMDSA
210 220 230 240 250
RLGGPCPPSS NSGISATCYG SGGRMEGPPP TYSEVIGHYP GSSFQHQQSS
260 270 280
GPPSLLEGTR LHHTHIAPLE SAAIWSKEKD KQKGHPL
Length:287
Mass (Da):31,609
Last modified:December 1, 2001 - v1
Checksum:i6103473561AE08DA
GO
Isoform 2 (identifier: Q969W9-2) [UniParc]FASTAAdd to basket
Also known as: b

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: MHRLMGVNSTAAAAAGQPNVSCTCNCKRSLFQSMEIT → MA

Show »
Length:252
Mass (Da):27,900
Checksum:i0864B9DAB8A21959
GO
Isoform 3 (identifier: Q969W9-3) [UniParc]FASTAAdd to basket
Also known as: c

The sequence of this isoform differs from the canonical sequence as follows:
     1-50: Missing.

Show »
Length:237
Mass (Da):26,201
Checksum:iA44A274EAABFD930
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_062154128E → D. Corresponds to variant dbSNP:rs41314918Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0445881 – 50Missing in isoform 3. 1 PublicationAdd BLAST50
Alternative sequenceiVSP_0064381 – 37MHRLM…SMEIT → MA in isoform 2. 1 PublicationAdd BLAST37

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF224278 mRNA Translation: AAF86322.1
AF305616 mRNA Translation: AAL16781.1
AY128643 mRNA Translation: AAM89277.1
AF305426 Genomic DNA Translation: AAL09357.1
AL035541 Genomic DNA No translation available.
AL121913 Genomic DNA No translation available.
CH471077 Genomic DNA Translation: EAW75505.1
CH471077 Genomic DNA Translation: EAW75508.1
BC015918 mRNA Translation: AAH15918.2
CCDSiCCDS13462.1 [Q969W9-2]
CCDS13463.1 [Q969W9-1]
CCDS13464.1 [Q969W9-3]
RefSeqiNP_001242905.1, NM_001255976.1
NP_064567.2, NM_020182.4 [Q969W9-1]
NP_954638.1, NM_199169.2 [Q969W9-2]
NP_954639.1, NM_199170.2 [Q969W9-3]
NP_954640.1, NM_199171.2 [Q969W9-3]
UniGeneiHs.517155

Genome annotation databases

EnsembliENST00000265626; ENSP00000265626; ENSG00000124225 [Q969W9-3]
ENST00000341744; ENSP00000345826; ENSG00000124225 [Q969W9-1]
ENST00000347215; ENSP00000344014; ENSG00000124225 [Q969W9-2]
ENST00000395814; ENSP00000379159; ENSG00000124225 [Q969W9-3]
ENST00000395816; ENSP00000379161; ENSG00000124225 [Q969W9-3]
GeneIDi56937
KEGGihsa:56937
UCSCiuc002xyq.5 human [Q969W9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPMEPA_HUMAN
AccessioniPrimary (citable) accession number: Q969W9
Secondary accession number(s): Q5TDR6
, Q8NER4, Q96B72, Q9UJD3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 5, 2002
Last sequence update: December 1, 2001
Last modified: March 28, 2018
This is version 132 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 20
    Human chromosome 20: 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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