Gene/Proteome Database (LMPD)

LMPD ID
LMP002386
Gene ID
56937
Species
Homo sapiens (Human)
Gene Name
prostate transmembrane protein, androgen induced 1
Gene Symbol
PMEPA1
Synonyms
STAG1; TMEPAI
Chromosome
20
Map Location
20q13.31-q13.33
Summary
This gene encodes a transmembrane protein that contains a Smad interacting motif (SIM). Expression of this gene is induced by androgens and transforming growth factor beta, and the encoded protein suppresses the androgen receptor and transforming growth factor beta signaling pathways though interactions with Smad proteins. Overexpression of this gene may play a role in multiple types of cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]
Orthologs
View orthologs and multiple alignments for PMEPA1

Proteins

protein TMEPAI isoform a
Refseq ID NP_064567
Protein GI 21361841
UniProt ID Q969W9
mRNA ID NM_020182
Length 287
RefSeq Status REVIEWED
MHRLMGVNSTAAAAAGQPNVSCTCNCKRSLFQSMEITELEFVQIIIIVVVMMVMVVVITCLLSHYKLSARSFISRHSQGRRREDALSSEGCLWPSESTVSGNGIPEPQVYAPPRPTDRLAVPPFAQRERFHRFQPTYPYLQHEIDLPPTISLSDGEEPPPYQGPCTLQLRDPEQQLELNRESVRAPPNRTIFDSDLMDSARLGGPCPPSSNSGISATCYGSGGRMEGPPPTYSEVIGHYPGSSFQHQQSSGPPSLLEGTRLHHTHIAPLESAAIWSKEKDKQKGHPL
protein TMEPAI isoform b
Refseq ID NP_954638
Protein GI 40317616
UniProt ID Q5JY37
mRNA ID NM_199169
Length 252
RefSeq Status REVIEWED
MAELEFVQIIIIVVVMMVMVVVITCLLSHYKLSARSFISRHSQGRRREDALSSEGCLWPSESTVSGNGIPEPQVYAPPRPTDRLAVPPFAQRERFHRFQPTYPYLQHEIDLPPTISLSDGEEPPPYQGPCTLQLRDPEQQLELNRESVRAPPNRTIFDSDLMDSARLGGPCPPSSNSGISATCYGSGGRMEGPPPTYSEVIGHYPGSSFQHQQSSGPPSLLEGTRLHHTHIAPLESAAIWSKEKDKQKGHPL
protein TMEPAI isoform c precursor
Refseq ID NP_954639
Protein GI 40317618
UniProt ID Q5JY37
mRNA ID NM_199170
Length 237
RefSeq Status REVIEWED
MMVMVVVITCLLSHYKLSARSFISRHSQGRRREDALSSEGCLWPSESTVSGNGIPEPQVYAPPRPTDRLAVPPFAQRERFHRFQPTYPYLQHEIDLPPTISLSDGEEPPPYQGPCTLQLRDPEQQLELNRESVRAPPNRTIFDSDLMDSARLGGPCPPSSNSGISATCYGSGGRMEGPPPTYSEVIGHYPGSSFQHQQSSGPPSLLEGTRLHHTHIAPLESAAIWSKEKDKQKGHPL
protein TMEPAI isoform c precursor
Refseq ID NP_954640
Protein GI 40317620
UniProt ID Q969W9
mRNA ID NM_199171
Length 237
RefSeq Status REVIEWED
Protein sequence is identical to GI:40317618 (mRNA isoform)
sig_peptide: 1..19 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2139 peptide sequence: MMVMVVVITCLLSHYKLSA sig_peptide: 1..19 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2139 peptide sequence: MMVMVVVITCLLSHYKLSA
protein TMEPAI isoform d
Refseq ID NP_001242905
Protein GI 364023812
UniProt ID Q969W9
mRNA ID NM_001255976
Length 259
RefSeq Status REVIEWED
MPAIPAHGAELEFVQIIIIVVVMMVMVVVITCLLSHYKLSARSFISRHSQGRRREDALSSEGCLWPSESTVSGNGIPEPQVYAPPRPTDRLAVPPFAQRERFHRFQPTYPYLQHEIDLPPTISLSDGEEPPPYQGPCTLQLRDPEQQLELNRESVRAPPNRTIFDSDLMDSARLGGPCPPSSNSGISATCYGSGGRMEGPPPTYSEVIGHYPGSSFQHQQSSGPPSLLEGTRLHHTHIAPLESAAIWSKEKDKQKGHPL

Gene Information

Entrez Gene ID
56937
Gene Name
prostate transmembrane protein, androgen induced 1
Gene Symbol
PMEPA1
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0031901 IDA:UniProtKB C early endosome membrane
GO:0010008 IDA:UniProtKB C endosome membrane
GO:0000139 IDA:UniProtKB C Golgi membrane
GO:0016021 IEA:UniProtKB-KW C integral component of membrane
GO:0016021 NAS:UniProtKB C integral component of membrane
GO:0005886 TAS:Reactome C plasma membrane
GO:0070412 IPI:UniProtKB F R-SMAD binding
GO:0050699 IPI:UniProtKB F WW domain binding
GO:0030521 NAS:UniProtKB P androgen receptor signaling pathway
GO:0060394 IDA:UniProtKB P negative regulation of pathway-restricted SMAD protein phosphorylation
GO:0010991 IDA:UniProtKB P negative regulation of SMAD protein complex assembly
GO:0030512 IDA:UniProtKB P negative regulation of transforming growth factor beta receptor signaling pathway
GO:0007179 TAS:Reactome P transforming growth factor beta receptor signaling pathway

REACTOME Pathway Links

REACTOME Pathway ID Description
REACT_116125 Disease
REACT_120727 Downregulation of TGF-beta receptor signaling
REACT_169398 Loss of Function of SMAD2/3 in Cancer
REACT_169219 Loss of Function of SMAD4 in Cancer
REACT_169311 Loss of Function of TGFBR1 in Cancer
REACT_169435 Loss of Function of TGFBR2 in Cancer
REACT_6844 Signaling by TGF-beta Receptor Complex
REACT_169122 Signaling by TGF-beta Receptor Complex in Cancer
REACT_111102 Signal Transduction
REACT_169165 SMAD2/3 MH2 Domain Mutants in Cancer
REACT_169103 SMAD2/3 Phosphorylation Motif Mutants in Cancer
REACT_169107 SMAD4 MH2 Domain Mutants in Cancer
REACT_120850 TGF-beta receptor signaling activates SMADs
REACT_169263 TGFBR1 KD Mutants in Cancer
REACT_169445 TGFBR1 LBD Mutants in Cancer
REACT_169440 TGFBR2 Kinase Domain Mutants in Cancer
REACT_169192 TGFBR2 MSI Frameshift Mutants in Cancer

Domain Information

InterPro Annotations

Accession Description

UniProt Annotations

Entry Information

Gene Name
prostate transmembrane protein, androgen induced 1
Protein Entry
PMEPA_HUMAN
UniProt ID
Q969W9
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=3; Name=1; Synonyms=a; IsoId=Q969W9-1; Sequence=Displayed; Name=2; Synonyms=b; IsoId=Q969W9-2; Sequence=VSP_006438; Name=3; Synonyms=c; IsoId=Q969W9-3; Sequence=VSP_044588;
Domain The SMAD interaction motif is required for interaction with SMAD2 and SMAD3 and the negative regulation of TGF-beta signaling. {ECO:0000269|PubMed:20129061}.
Domain The WW-binding motifs mediate interaction with NEDD4. {ECO:0000269|PubMed:18703514}.
Function 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). {ECO:0000269|PubMed:18703514, ECO:0000269|PubMed:20129061, ECO:0000269|PubMed:24627487}.
Induction Up-regulated by androgen and TGF-beta (at protein level). {ECO:0000269|PubMed:18703514, ECO:0000269|PubMed:20129061}.
Similarity Belongs to the PMEPA1 family. {ECO:0000305}.
Subcellular Location Early endosome membrane; Single-pass membrane protein. Golgi apparatus membrane; Single-pass membrane protein.
Subunit Interacts with NEDD4 (WW-binding motifs). Interacts with AR. Interacts with LDLRAD4. Interacts (via the SMAD interaction motif) with SMAD2 and SMAD3. {ECO:0000269|PubMed:12907594, ECO:0000269|PubMed:18703514, ECO:0000269|PubMed:20129061, ECO:0000269|PubMed:24627487}.
Tissue Specificity Highest expression in prostate. Also expressed in ovary.

Identical and Related Proteins

Unique RefSeq proteins for LMP002386 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
21361841 RefSeq NP_064567 287 protein TMEPAI isoform a
40317616 RefSeq NP_954638 252 protein TMEPAI isoform b
40317618 RefSeq NP_954639 237 protein TMEPAI isoform c precursor
364023812 RefSeq NP_001242905 259 protein TMEPAI isoform d

Identical Sequences to LMP002386 proteins

Reference Database Accession Length Protein Name
GI:21361841 DBBJ BAI47150.1 287 prostate transmembrane protein, androgen induced 1, partial [synthetic construct]
GI:21361841 EMBL CAE11644.1 287 unnamed protein product [Homo sapiens]
GI:40317618 GenBank EAW75505.1 237 transmembrane, prostate androgen induced RNA, isoform CRA_b [Homo sapiens]
GI:21361841 GenBank EAW75507.1 287 transmembrane, prostate androgen induced RNA, isoform CRA_d [Homo sapiens]
GI:40317618 GenBank EAW75508.1 237 transmembrane, prostate androgen induced RNA, isoform CRA_b [Homo sapiens]
GI:40317616 GenBank ADS62787.1 252 Sequence 3 from patent US 7807785
GI:40317616 GenBank AEF74519.1 252 Sequence 100 from patent US 7939268
GI:40317616 GenBank AEF74520.1 252 Sequence 101 from patent US 7939268
GI:21361841 GenBank AEF74535.1 287 Sequence 120 from patent US 7939268
GI:40317616 GenBank AEH18178.1 252 Sequence 100 from patent US 7951546
GI:40317616 GenBank AEH18179.1 252 Sequence 101 from patent US 7951546
GI:21361841 GenBank AEH18194.1 287 Sequence 120 from patent US 7951546
GI:21361841 GenBank AHD77421.1 287 Sequence 22554 from patent US 8586006
GI:40317616 GenBank AHD77422.1 252 Sequence 22555 from patent US 8586006
GI:40317618 GenBank AHD77423.1 237 Sequence 22556 from patent US 8586006
GI:40317618 GenBank AHD77424.1 237 Sequence 22557 from patent US 8586006
GI:40317618 GenBank AIC63509.1 237 PMEPA1, partial [synthetic construct]
GI:40317618 RefSeq NP_954640.1 237 protein TMEPAI isoform c precursor [Homo sapiens]

Related Sequences to LMP002386 proteins

Reference Database Accession Length Protein Name
GI:364023812 DBBJ BAG58927.1 252 unnamed protein product [Homo sapiens]
GI:40317618 DBBJ BAI47150.1 287 prostate transmembrane protein, androgen induced 1, partial [synthetic construct]
GI:40317616 DBBJ BAI47150.1 287 prostate transmembrane protein, androgen induced 1, partial [synthetic construct]
GI:40317618 EMBL CAD29005.1 287 unnamed protein product [Homo sapiens]
GI:40317618 EMBL CAD29006.1 287 unnamed protein product, partial [Homo sapiens]
GI:364023812 EMBL CAE11643.1 252 unnamed protein product [Homo sapiens]
GI:40317618 EMBL CAE11644.1 287 unnamed protein product [Homo sapiens]
GI:40317618 GenBank AAL16781.1 287 STAG1/PMEPA1 [Homo sapiens]
GI:40317616 GenBank AAL16781.1 287 STAG1/PMEPA1 [Homo sapiens]
GI:364023812 GenBank AAQ31902.1 252 Sequence 3 from patent US 6566130
GI:364023812 GenBank ACS08292.1 252 Sequence 3 from patent US 7537896
GI:21361841 GenBank JAA20988.1 287 prostate transmembrane protein, androgen induced 1 [Pan troglodytes]
GI:21361841 GenBank JAA32948.1 287 prostate transmembrane protein, androgen induced 1 [Pan troglodytes]
GI:21361841 GenBank JAA40889.1 287 prostate transmembrane protein, androgen induced 1 [Pan troglodytes]
GI:40317618 GenBank AHD77421.1 287 Sequence 22554 from patent US 8586006
GI:364023812 GenBank AHD77422.1 252 Sequence 22555 from patent US 8586006
GI:40317616 RefSeq XP_002830508.1 252 PREDICTED: transmembrane prostate androgen-induced protein isoform X1 [Pongo abelii]
GI:40317616 RefSeq XP_003253026.1 296 PREDICTED: transmembrane prostate androgen-induced protein isoform 1 [Nomascus leucogenys]
GI:40317616 RefSeq NP_001242905.1 259 protein TMEPAI isoform d [Homo sapiens]
GI:40317616 RefSeq XP_003806217.1 252 PREDICTED: transmembrane prostate androgen-induced protein [Pan paniscus]
GI:21361841 RefSeq XP_003904617.1 287 PREDICTED: transmembrane prostate androgen-induced protein isoform X1 [Papio anubis]
GI:364023812 RefSeq XP_004090104.1 274 PREDICTED: transmembrane prostate androgen-induced protein [Nomascus leucogenys]
GI:21361841 RefSeq XP_005569488.1 287 PREDICTED: transmembrane prostate androgen-induced protein isoform X1 [Macaca fascicularis]
GI:21361841 RefSeq XP_009435732.1 287 PREDICTED: LOW QUALITY PROTEIN: transmembrane prostate androgen-induced protein [Pan troglodytes]