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Protein

Tetraspanin-12

Gene

TSPAN12

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

Functioni

Regulator of cell surface receptor signal transduction. Plays a central role in retinal vascularization by regulating norrin (NDP) signal transduction. Acts in concert with norrin (NDP) to promote FZD4 multimerization and subsequent activation of FZD4, leading to promote accumulation of beta-catenin (CTNNB1) and stimulate LEF/TCF-mediated transcriptional programs. Suprisingly, it only activate the norrin (NDP)-dependent activation of FZD4, while it does not activate the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1) (By similarity). Acts as a regulator of membrane proteinases such as ADAM10 and MMP14/MT1-MMP. Activates ADAM10-dependent cleavage activity of amyloid precursor protein (APP). Activates MMP14/MT1-MMP-dependent cleavage activity.By similarity2 Publications

GO - Biological processi

Keywordsi

Biological processAngiogenesis

Enzyme and pathway databases

SIGNORiO95859

Protein family/group databases

TCDBi8.A.40.1.20 the tetraspanin (tetraspanin) family

Names & Taxonomyi

Protein namesi
Recommended name:
Tetraspanin-12
Short name:
Tspan-12
Alternative name(s):
Tetraspan NET-2
Transmembrane 4 superfamily member 12
Gene namesi
Name:TSPAN12
Synonyms:NET2, TM4SF12
ORF Names:UNQ774/PRO1568
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000106025.8
HGNCiHGNC:21641 TSPAN12
MIMi613138 gene
neXtProtiNX_O95859

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 – 12CytoplasmicSequence analysisAdd BLAST12
Transmembranei13 – 33HelicalSequence analysisAdd BLAST21
Topological domaini34 – 59ExtracellularSequence analysisAdd BLAST26
Transmembranei60 – 80HelicalSequence analysisAdd BLAST21
Topological domaini81 – 89CytoplasmicSequence analysis9
Transmembranei90 – 110HelicalSequence analysisAdd BLAST21
Topological domaini111 – 224ExtracellularSequence analysisAdd BLAST114
Transmembranei225 – 245HelicalSequence analysisAdd BLAST21
Topological domaini246 – 305CytoplasmicSequence analysisAdd BLAST60

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Vitreoretinopathy, exudative 5 (EVR5)3 Publications
The disease is caused by mutations affecting the gene represented in this entry. TSPAN12 dominant and recessive mutations have been identified in patients with exudative vitreoretinopathy. Patients with mutations in both alleles of TSPAN12 have severe exudative vitreoretinopathy or retinal dysplasia. These mutations appear to result in a milder phenotype in heterozygous mutation carriers (PubMed:22427576).1 Publication
Disease descriptionA disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery.
See also OMIM:613310
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06889949T → M in EVR5. 1 PublicationCorresponds to variant dbSNP:rs538591733EnsemblClinVar.1
Natural variantiVAR_063576101L → H in EVR5. 1 PublicationCorresponds to variant dbSNP:rs267607152EnsemblClinVar.1
Natural variantiVAR_068900138Y → C in EVR5. 1 PublicationCorresponds to variant dbSNP:rs587777283EnsemblClinVar.1
Natural variantiVAR_063577188G → R in EVR5. 1 PublicationCorresponds to variant dbSNP:rs267607151EnsemblClinVar.1
Natural variantiVAR_063578210M → R in EVR5. 1 Publication1
Natural variantiVAR_068901223L → P in EVR5. 1 Publication1
Natural variantiVAR_063579237A → P in EVR5. 1 PublicationCorresponds to variant dbSNP:rs267607154EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi9C → S: Impairs interaction with ADAM10; when associated with S-12 and S-83. 1 Publication1
Mutagenesisi12C → S: Impairs interaction with ADAM10; when associated with S-9 and S-83. 1 Publication1
Mutagenesisi83C → S: Impairs interaction with ADAM10; when associated with S-9 and S-12. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi23554
GeneReviewsiTSPAN12
MalaCardsiTSPAN12
MIMi613310 phenotype
OpenTargetsiENSG00000106025
Orphaneti891 Familial exudative vitreoretinopathy
PharmGKBiPA134954047

Polymorphism and mutation databases

BioMutaiTSPAN12

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002192571 – 305Tetraspanin-12Add BLAST305

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi9S-palmitoyl cysteineBy similarity1
Lipidationi12S-palmitoyl cysteineBy similarity1
Lipidationi83S-palmitoyl cysteineBy similarity1

Post-translational modificationi

Palmitoylated; required for interaction with ADAM10. The precise position of palmitoylated residues is unclear and occurs either on Cys-9, Cys-12 and/or Cys-83.1 Publication

Keywords - PTMi

Lipoprotein, Palmitate

Proteomic databases

MaxQBiO95859
PaxDbiO95859
PRIDEiO95859
ProteomicsDBi51092
51093 [O95859-2]

PTM databases

iPTMnetiO95859
PhosphoSitePlusiO95859
SwissPalmiO95859

Expressioni

Gene expression databases

BgeeiENSG00000106025 Expressed in 209 organ(s), highest expression level in right adrenal gland
CleanExiHS_TSPAN12
ExpressionAtlasiO95859 baseline and differential
GenevisibleiO95859 HS

Organism-specific databases

HPAiHPA051570
HPA058244

Interactioni

Subunit structurei

Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP) (By similarity). Interacts (when palmitoylated) with ADAM10. Interacts with MMP14/MT1-MMP.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
TFCP2Q128003EBI-2466403,EBI-717422

Protein-protein interaction databases

BioGridi117098, 1 interactor
IntActiO95859, 21 interactors
STRINGi9606.ENSP00000222747

Structurei

3D structure databases

ProteinModelPortaliO95859
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the tetraspanin (TM4SF) family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3882 Eukaryota
ENOG4111IRY LUCA
GeneTreeiENSGT00510000047764
HOGENOMiHOG000252919
HOVERGENiHBG054253
InParanoidiO95859
KOiK17355
OMAiTQHLSCH
OrthoDBiEOG091G0G2A
PhylomeDBiO95859
TreeFamiTF316345

Family and domain databases

Gene3Di1.10.1450.10, 1 hit
InterProiView protein in InterPro
IPR000301 Tetraspanin
IPR018499 Tetraspanin/Peripherin
IPR018503 Tetraspanin_CS
IPR008952 Tetraspanin_EC2_sf
PfamiView protein in Pfam
PF00335 Tetraspannin, 1 hit
PIRSFiPIRSF002419 Tetraspanin, 1 hit
PRINTSiPR00259 TMFOUR
SUPFAMiSSF48652 SSF48652, 1 hit
PROSITEiView protein in PROSITE
PS00421 TM4_1, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O95859-1) [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
MAREDSVKCL RCLLYALNLL FWLMSISVLA VSAWMRDYLN NVLTLTAETR
60 70 80 90 100
VEEAVILTYF PVVHPVMIAV CCFLIIVGML GYCGTVKRNL LLLAWYFGSL
110 120 130 140 150
LVIFCVELAC GVWTYEQELM VPVQWSDMVT LKARMTNYGL PRYRWLTHAW
160 170 180 190 200
NFFQREFKCC GVVYFTDWLE MTEMDWPPDS CCVREFPGCS KQAHQEDLSD
210 220 230 240 250
LYQEGCGKKM YSFLRGTKQL QVLRFLGISI GVTQILAMIL TITLLWALYY
260 270 280 290 300
DRREPGTDQM MSLKNDNSQH LSCPSVELLK PSLSRIFEHT SMANSFNTHF

EMEEL
Length:305
Mass (Da):35,383
Last modified:May 1, 1999 - v1
Checksum:iEBF4D5E1371E92DC
GO
Isoform 2 (identifier: O95859-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-120: MAREDSVKCL...GVWTYEQELM → MAHKLLL

Note: No experimental confirmation available.
Show »
Length:192
Mass (Da):22,511
Checksum:iE789CE4F377F3F17
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J9U1C9J9U1_HUMAN
Tetraspanin-12
TSPAN12
147Annotation score:
C9IZ82C9IZ82_HUMAN
Tetraspanin-12
TSPAN12
120Annotation score:
C9JC05C9JC05_HUMAN
Tetraspanin-12
TSPAN12
112Annotation score:
C9JQM0C9JQM0_HUMAN
Tetraspanin-12
TSPAN12
95Annotation score:
H7C0X9H7C0X9_HUMAN
Tetraspanin-12
TSPAN12
42Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06889949T → M in EVR5. 1 PublicationCorresponds to variant dbSNP:rs538591733EnsemblClinVar.1
Natural variantiVAR_06225357L → S1 PublicationCorresponds to variant dbSNP:rs17852934Ensembl.1
Natural variantiVAR_063576101L → H in EVR5. 1 PublicationCorresponds to variant dbSNP:rs267607152EnsemblClinVar.1
Natural variantiVAR_068900138Y → C in EVR5. 1 PublicationCorresponds to variant dbSNP:rs587777283EnsemblClinVar.1
Natural variantiVAR_063577188G → R in EVR5. 1 PublicationCorresponds to variant dbSNP:rs267607151EnsemblClinVar.1
Natural variantiVAR_063578210M → R in EVR5. 1 Publication1
Natural variantiVAR_068901223L → P in EVR5. 1 Publication1
Natural variantiVAR_063579237A → P in EVR5. 1 PublicationCorresponds to variant dbSNP:rs267607154EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0385251 – 120MARED…EQELM → MAHKLLL in isoform 2. 1 PublicationAdd BLAST120

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF124522 mRNA Translation: AAD17317.1
AY358703 mRNA Translation: AAQ89066.1
AK299247 mRNA Translation: BAG61278.1
AK312239 mRNA Translation: BAG35172.1
AC004456 Genomic DNA Translation: AAQ96879.1
CH236947 Genomic DNA Translation: EAL24349.1
BC031265 mRNA Translation: AAH31265.1
CCDSiCCDS5777.1 [O95859-1]
RefSeqiNP_036470.1, NM_012338.3 [O95859-1]
XP_005250296.1, XM_005250239.2 [O95859-1]
XP_011514295.1, XM_011515993.1 [O95859-1]
XP_011514296.1, XM_011515994.1 [O95859-1]
XP_016867401.1, XM_017011912.1
UniGeneiHs.16529

Genome annotation databases

EnsembliENST00000222747; ENSP00000222747; ENSG00000106025 [O95859-1]
ENST00000415871; ENSP00000397699; ENSG00000106025 [O95859-1]
GeneIDi23554
KEGGihsa:23554
UCSCiuc003vjk.4 human [O95859-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF124522 mRNA Translation: AAD17317.1
AY358703 mRNA Translation: AAQ89066.1
AK299247 mRNA Translation: BAG61278.1
AK312239 mRNA Translation: BAG35172.1
AC004456 Genomic DNA Translation: AAQ96879.1
CH236947 Genomic DNA Translation: EAL24349.1
BC031265 mRNA Translation: AAH31265.1
CCDSiCCDS5777.1 [O95859-1]
RefSeqiNP_036470.1, NM_012338.3 [O95859-1]
XP_005250296.1, XM_005250239.2 [O95859-1]
XP_011514295.1, XM_011515993.1 [O95859-1]
XP_011514296.1, XM_011515994.1 [O95859-1]
XP_016867401.1, XM_017011912.1
UniGeneiHs.16529

3D structure databases

ProteinModelPortaliO95859
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117098, 1 interactor
IntActiO95859, 21 interactors
STRINGi9606.ENSP00000222747

Protein family/group databases

TCDBi8.A.40.1.20 the tetraspanin (tetraspanin) family

PTM databases

iPTMnetiO95859
PhosphoSitePlusiO95859
SwissPalmiO95859

Polymorphism and mutation databases

BioMutaiTSPAN12

Proteomic databases

MaxQBiO95859
PaxDbiO95859
PRIDEiO95859
ProteomicsDBi51092
51093 [O95859-2]

Protocols and materials databases

DNASUi23554
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000222747; ENSP00000222747; ENSG00000106025 [O95859-1]
ENST00000415871; ENSP00000397699; ENSG00000106025 [O95859-1]
GeneIDi23554
KEGGihsa:23554
UCSCiuc003vjk.4 human [O95859-1]

Organism-specific databases

CTDi23554
DisGeNETi23554
EuPathDBiHostDB:ENSG00000106025.8
GeneCardsiTSPAN12
GeneReviewsiTSPAN12
HGNCiHGNC:21641 TSPAN12
HPAiHPA051570
HPA058244
MalaCardsiTSPAN12
MIMi613138 gene
613310 phenotype
neXtProtiNX_O95859
OpenTargetsiENSG00000106025
Orphaneti891 Familial exudative vitreoretinopathy
PharmGKBiPA134954047
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3882 Eukaryota
ENOG4111IRY LUCA
GeneTreeiENSGT00510000047764
HOGENOMiHOG000252919
HOVERGENiHBG054253
InParanoidiO95859
KOiK17355
OMAiTQHLSCH
OrthoDBiEOG091G0G2A
PhylomeDBiO95859
TreeFamiTF316345

Enzyme and pathway databases

SIGNORiO95859

Miscellaneous databases

ChiTaRSiTSPAN12 human
GeneWikiiTSPAN12
GenomeRNAii23554
PROiPR:O95859
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106025 Expressed in 209 organ(s), highest expression level in right adrenal gland
CleanExiHS_TSPAN12
ExpressionAtlasiO95859 baseline and differential
GenevisibleiO95859 HS

Family and domain databases

Gene3Di1.10.1450.10, 1 hit
InterProiView protein in InterPro
IPR000301 Tetraspanin
IPR018499 Tetraspanin/Peripherin
IPR018503 Tetraspanin_CS
IPR008952 Tetraspanin_EC2_sf
PfamiView protein in Pfam
PF00335 Tetraspannin, 1 hit
PIRSFiPIRSF002419 Tetraspanin, 1 hit
PRINTSiPR00259 TMFOUR
SUPFAMiSSF48652 SSF48652, 1 hit
PROSITEiView protein in PROSITE
PS00421 TM4_1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTSN12_HUMAN
AccessioniPrimary (citable) accession number: O95859
Secondary accession number(s): A4D0V8
, B4DRG6, Q549U9, Q8N5Y0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 1999
Last modified: November 7, 2018
This is version 138 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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