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Protein

Tomoregulin-2

Gene

TMEFF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May be a survival factor for hippocampal and mesencephalic neurons. The shedded form up-regulates cancer cell proliferation, probably by promoting ERK1/2 phosphorylation.2 Publications

GO - Biological processi

  • negative regulation of cell migration Source: MGI
  • negative regulation of integrin biosynthetic process Source: MGI
  • negative regulation of stress fiber assembly Source: MGI
  • wound healing, spreading of cells Source: MGI
Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:ENSG00000144339-MONOMER.

Protein family/group databases

MEROPSiI01.969.

Names & Taxonomyi

Protein namesi
Recommended name:
Tomoregulin-2
Short name:
TR-2
Alternative name(s):
Hyperplastic polyposis protein 1
Transmembrane protein with EGF-like and two follistatin-like domains
Gene namesi
Name:TMEFF2
Synonyms:HPP1, TENB2, TPEF
ORF Names:UNQ178/PRO204
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:11867. TMEFF2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini41 – 320ExtracellularSequence analysisAdd BLAST280
Transmembranei321 – 341HelicalSequence analysisAdd BLAST21
Topological domaini342 – 374CytoplasmicSequence analysisAdd BLAST33

GO - Cellular componenti

  • extracellular region Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi23671.
OpenTargetsiENSG00000144339.
PharmGKBiPA36568.

Polymorphism and mutation databases

BioMutaiTMEFF2.
DMDMi71153590.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 401 PublicationAdd BLAST40
ChainiPRO_000001658741 – 374Tomoregulin-2Add BLAST334

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi55N-linked (GlcNAc...)Sequence analysis1
Glycosylationi204N-linked (GlcNAc...) (complex); atypical1 Publication1
Glycosylationi230N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi265 ↔ 278By similarity
Disulfide bondi273 ↔ 289By similarity
Disulfide bondi291 ↔ 300By similarity

Post-translational modificationi

N-glycosylated. Contains chondroitin sulfate glycosaminoglycans.2 Publications
A soluble form (TMEFF2-ECD) is produced by proteolytic shedding. This shedding can be induced by phorbol ester or proinflammatory cytokines such as TNFalpha, and is mediated by ADAM17.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9UIK5.
PeptideAtlasiQ9UIK5.
PRIDEiQ9UIK5.

PTM databases

iPTMnetiQ9UIK5.
PhosphoSitePlusiQ9UIK5.

Miscellaneous databases

PMAP-CutDBQ9UIK5.

Expressioni

Tissue specificityi

Highly expressed in adult and fetal brain, spinal cord and prostate. Expressed in all brain regions except the pituitary gland, with highest levels in amygdala and corpus callosum. Expressed in the pericryptal myofibroblasts and other stromal cells of normal colonic mucosa. Expressed in prostate carcinoma. Down-regulated in colorectal cancer. Present in Alzheimer disease plaques (at protein level). Isoform 3 is expressed weakly in testis and at high levels in normal and cancerous prostate.6 Publications

Inductioni

Down-regulated in tumor cell lines in response to a high level of methylation in the 5' region. The CpG island methylation correlates with TMEFF2 silencing in tumor cell lines.2 Publications

Gene expression databases

BgeeiENSG00000144339.
GenevisibleiQ9UIK5. HS.

Organism-specific databases

HPAiHPA015587.

Interactioni

Protein-protein interaction databases

BioGridi117189. 1 interactor.
IntActiQ9UIK5. 2 interactors.
STRINGi9606.ENSP00000272771.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FMWmodel-A264-301[»]
ProteinModelPortaliQ9UIK5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini85 – 137Kazal-like 1PROSITE-ProRule annotationAdd BLAST53
Domaini176 – 229Kazal-like 2PROSITE-ProRule annotationAdd BLAST54
Domaini261 – 301EGF-likePROSITE-ProRule annotationAdd BLAST41

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni303 – 320Required for sheddingAdd BLAST18

Sequence similaritiesi

Belongs to the tomoregulin family.Curated
Contains 1 EGF-like domain.PROSITE-ProRule annotation
Contains 2 Kazal-like domains.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IP0A. Eukaryota.
ENOG4110TEU. LUCA.
GeneTreeiENSGT00730000110884.
HOVERGENiHBG053816.
InParanoidiQ9UIK5.
OMAiENTMRAS.
OrthoDBiEOG091G0AKU.
PhylomeDBiQ9UIK5.
TreeFamiTF330868.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR002350. Kazal_dom.
[Graphical view]
PfamiPF07648. Kazal_2. 2 hits.
[Graphical view]
SMARTiSM00280. KAZAL. 2 hits.
[Graphical view]
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS51465. KAZAL_2. 2 hits.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q9UIK5-1) [UniParc]FASTAAdd to basket

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
MVLWESPRQC SSWTLCEGFC WLLLLPVMLL IVARPVKLAA FPTSLSDCQT
60 70 80 90 100
PTGWNCSGYD DRENDLFLCD TNTCKFDGEC LRIGDTVTCV CQFKCNNDYV
110 120 130 140 150
PVCGSNGESY QNECYLRQAA CKQQSEILVV SEGSCATDAG SGSGDGVHEG
160 170 180 190 200
SGETSQKETS TCDICQFGAE CDEDAEDVWC VCNIDCSQTN FNPLCASDGK
210 220 230 240 250
SYDNACQIKE ASCQKQEKIE VMSLGRCQDN TTTTTKSEDG HYARTDYAEN
260 270 280 290 300
ANKLEESARE HHIPCPEHYN GFCMHGKCEH SINMQEPSCR CDAGYTGQHC
310 320 330 340 350
EKKDYSVLYV VPGPVRFQYV LIAAVIGTIQ IAVICVVVLC ITRKCPRSNR
360 370
IHRQKQNTGH YSSDNTTRAS TRLI
Length:374
Mass (Da):41,428
Last modified:May 1, 2000 - v1
Checksum:i44452F680FEBDCDB
GO
Isoform 2 (identifier: Q9UIK5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     344-346: KCP → AKL
     347-374: Missing.

Show »
Length:346
Mass (Da):38,132
Checksum:iA2C7231AD4CD43EA
GO
Isoform 3 (identifier: Q9UIK5-3) [UniParc]FASTAAdd to basket
Also known as: TMEFF2-S

The sequence of this isoform differs from the canonical sequence as follows:
     147-175: VHEGSGETSQKETSTCDICQFGAECDEDA → GRSCLFTYLKIYWWILLCIFTYVCSISDI
     176-374: Missing.

Show »
Length:175
Mass (Da):19,472
Checksum:i8CF92F9D9FB171DF
GO

Sequence cautioni

The sequence BAA90820 differs from that shown. Contaminating sequence. Mitochondrial contamination starting in position 361.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti28M → V in BAD96411 (Ref. 8) Curated1
Sequence conflicti63E → G in BAC11030 (PubMed:14702039).Curated1
Sequence conflicti222M → T in BAD96411 (Ref. 8) Curated1
Sequence conflicti339L → H in BAD96411 (Ref. 8) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_024973147 – 175VHEGS…CDEDA → GRSCLFTYLKIYWWILLCIF TYVCSISDI in isoform 3. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_024974176 – 374Missing in isoform 3. 1 PublicationAdd BLAST199
Alternative sequenceiVSP_014312344 – 346KCP → AKL in isoform 2. 2 Publications3
Alternative sequenceiVSP_014313347 – 374Missing in isoform 2. 2 PublicationsAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB017269 mRNA. Translation: BAA87897.1.
AF242221 Genomic DNA. Translation: AAG49451.1.
AF242222 mRNA. Translation: AAG49452.1.
AF179274 mRNA. Translation: AAD55776.2.
DQ133599 mRNA. Translation: AAZ43216.1.
AY358907 mRNA. Translation: AAQ89266.1.
AK074507 mRNA. Translation: BAC11030.1.
CR457390 mRNA. Translation: CAG33671.1.
AK222691 mRNA. Translation: BAD96411.1.
AL157430 mRNA. Translation: CAB75654.1.
AC092644 Genomic DNA. Translation: AAY14874.1.
AC098617 Genomic DNA. Translation: AAX88893.1.
BC008973 mRNA. Translation: AAH08973.1.
AB004064 mRNA. Translation: BAA90820.1. Different termination.
AF264150 Genomic DNA. Translation: AAF91397.1.
CCDSiCCDS2314.1. [Q9UIK5-1]
CCDS82547.1. [Q9UIK5-3]
CCDS82548.1. [Q9UIK5-2]
PIRiT46914.
RefSeqiNP_001292063.1. NM_001305134.1. [Q9UIK5-2]
NP_001292074.1. NM_001305145.1. [Q9UIK5-3]
NP_057276.2. NM_016192.3. [Q9UIK5-1]
UniGeneiHs.144513.

Genome annotation databases

EnsembliENST00000272771; ENSP00000272771; ENSG00000144339. [Q9UIK5-1]
ENST00000392314; ENSP00000376128; ENSG00000144339. [Q9UIK5-2]
ENST00000409056; ENSP00000386871; ENSG00000144339. [Q9UIK5-3]
GeneIDi23671.
KEGGihsa:23671.
UCSCiuc002utc.4. human. [Q9UIK5-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB017269 mRNA. Translation: BAA87897.1.
AF242221 Genomic DNA. Translation: AAG49451.1.
AF242222 mRNA. Translation: AAG49452.1.
AF179274 mRNA. Translation: AAD55776.2.
DQ133599 mRNA. Translation: AAZ43216.1.
AY358907 mRNA. Translation: AAQ89266.1.
AK074507 mRNA. Translation: BAC11030.1.
CR457390 mRNA. Translation: CAG33671.1.
AK222691 mRNA. Translation: BAD96411.1.
AL157430 mRNA. Translation: CAB75654.1.
AC092644 Genomic DNA. Translation: AAY14874.1.
AC098617 Genomic DNA. Translation: AAX88893.1.
BC008973 mRNA. Translation: AAH08973.1.
AB004064 mRNA. Translation: BAA90820.1. Different termination.
AF264150 Genomic DNA. Translation: AAF91397.1.
CCDSiCCDS2314.1. [Q9UIK5-1]
CCDS82547.1. [Q9UIK5-3]
CCDS82548.1. [Q9UIK5-2]
PIRiT46914.
RefSeqiNP_001292063.1. NM_001305134.1. [Q9UIK5-2]
NP_001292074.1. NM_001305145.1. [Q9UIK5-3]
NP_057276.2. NM_016192.3. [Q9UIK5-1]
UniGeneiHs.144513.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FMWmodel-A264-301[»]
ProteinModelPortaliQ9UIK5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117189. 1 interactor.
IntActiQ9UIK5. 2 interactors.
STRINGi9606.ENSP00000272771.

Protein family/group databases

MEROPSiI01.969.

PTM databases

iPTMnetiQ9UIK5.
PhosphoSitePlusiQ9UIK5.

Polymorphism and mutation databases

BioMutaiTMEFF2.
DMDMi71153590.

Proteomic databases

PaxDbiQ9UIK5.
PeptideAtlasiQ9UIK5.
PRIDEiQ9UIK5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000272771; ENSP00000272771; ENSG00000144339. [Q9UIK5-1]
ENST00000392314; ENSP00000376128; ENSG00000144339. [Q9UIK5-2]
ENST00000409056; ENSP00000386871; ENSG00000144339. [Q9UIK5-3]
GeneIDi23671.
KEGGihsa:23671.
UCSCiuc002utc.4. human. [Q9UIK5-1]

Organism-specific databases

CTDi23671.
DisGeNETi23671.
GeneCardsiTMEFF2.
HGNCiHGNC:11867. TMEFF2.
HPAiHPA015587.
MIMi605734. gene.
neXtProtiNX_Q9UIK5.
OpenTargetsiENSG00000144339.
PharmGKBiPA36568.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IP0A. Eukaryota.
ENOG4110TEU. LUCA.
GeneTreeiENSGT00730000110884.
HOVERGENiHBG053816.
InParanoidiQ9UIK5.
OMAiENTMRAS.
OrthoDBiEOG091G0AKU.
PhylomeDBiQ9UIK5.
TreeFamiTF330868.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000144339-MONOMER.

Miscellaneous databases

ChiTaRSiTMEFF2. human.
GeneWikiiTMEFF2.
GenomeRNAii23671.
PMAP-CutDBQ9UIK5.
PROiQ9UIK5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000144339.
GenevisibleiQ9UIK5. HS.

Family and domain databases

InterProiIPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR002350. Kazal_dom.
[Graphical view]
PfamiPF07648. Kazal_2. 2 hits.
[Graphical view]
SMARTiSM00280. KAZAL. 2 hits.
[Graphical view]
PROSITEiPS00022. EGF_1. 1 hit.
PS01186. EGF_2. 1 hit.
PS50026. EGF_3. 1 hit.
PS51465. KAZAL_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTEFF2_HUMAN
AccessioniPrimary (citable) accession number: Q9UIK5
Secondary accession number(s): Q2FA44
, Q4ZFW4, Q53H90, Q53RE1, Q8N2R5, Q9NR15, Q9NSS5, Q9P2Y9, Q9UK65
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 137 of the entry and version 1 of the sequence. [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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.