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O95859 (TSN12_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 110. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tetraspanin-12

Short name=Tspan-12
Alternative name(s):
Tetraspan NET-2
Transmembrane 4 superfamily member 12
Gene names
Name:TSPAN12
Synonyms:NET2, TM4SF12
ORF Names:UNQ774/PRO1568
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length305 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.7 Ref.8

Subunit structure

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. Ref.7

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity.

Post-translational modification

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. Ref.7

Involvement in disease

Vitreoretinopathy, exudative 5 (EVR5) [MIM:613310]: A 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.
Note: 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 (Ref.11). Ref.9 Ref.10 Ref.11

Sequence similarities

Belongs to the tetraspanin (TM4SF) family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95859-1)

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.
Isoform 2 (identifier: O95859-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-120: MAREDSVKCL...GVWTYEQELM → MAHKLLL
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 305305Tetraspanin-12
PRO_0000219257

Regions

Topological domain1 – 1212Cytoplasmic Potential
Transmembrane13 – 3321Helical; Potential
Topological domain34 – 5926Extracellular Potential
Transmembrane60 – 8021Helical; Potential
Topological domain81 – 899Cytoplasmic Potential
Transmembrane90 – 11021Helical; Potential
Topological domain111 – 224114Extracellular Potential
Transmembrane225 – 24521Helical; Potential
Topological domain246 – 30560Cytoplasmic Potential

Amino acid modifications

Lipidation91S-palmitoyl cysteine By similarity
Lipidation121S-palmitoyl cysteine By similarity
Lipidation831S-palmitoyl cysteine By similarity

Natural variations

Alternative sequence1 – 120120MARED…EQELM → MAHKLLL in isoform 2.
VSP_038525
Natural variant491T → M in EVR5. Ref.11
VAR_068899
Natural variant571L → S. Ref.6
Corresponds to variant rs17852934 [ dbSNP | Ensembl ].
VAR_062253
Natural variant1011L → H in EVR5. Ref.10
VAR_063576
Natural variant1381Y → C in EVR5. Ref.11
VAR_068900
Natural variant1881G → R in EVR5. Ref.9
VAR_063577
Natural variant2101M → R in EVR5. Ref.10
VAR_063578
Natural variant2231L → P in EVR5. Ref.11
VAR_068901
Natural variant2371A → P in EVR5. Ref.9
VAR_063579

Experimental info

Mutagenesis91C → S: Impairs interaction with ADAM10; when associated with S-12 and S-83. Ref.7
Mutagenesis121C → S: Impairs interaction with ADAM10; when associated with S-9 and S-83. Ref.7
Mutagenesis831C → S: Impairs interaction with ADAM10; when associated with S-9 and S-12. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: EBF4D5E1371E92DC

FASTA30535,383
        10         20         30         40         50         60 
MAREDSVKCL RCLLYALNLL FWLMSISVLA VSAWMRDYLN NVLTLTAETR VEEAVILTYF 

        70         80         90        100        110        120 
PVVHPVMIAV CCFLIIVGML GYCGTVKRNL LLLAWYFGSL LVIFCVELAC GVWTYEQELM 

       130        140        150        160        170        180 
VPVQWSDMVT LKARMTNYGL PRYRWLTHAW NFFQREFKCC GVVYFTDWLE MTEMDWPPDS 

       190        200        210        220        230        240 
CCVREFPGCS KQAHQEDLSD LYQEGCGKKM YSFLRGTKQL QVLRFLGISI GVTQILAMIL 

       250        260        270        280        290        300 
TITLLWALYY DRREPGTDQM MSLKNDNSQH LSCPSVELLK PSLSRIFEHT SMANSFNTHF 


EMEEL 

« Hide

Isoform 2 [UniParc].

Checksum: E789CE4F377F3F17
Show »

FASTA19222,511

References

« Hide 'large scale' references
[1]"Sequence and expression of seven new tetraspans."
Serru V., Dessen P., Boucheix C., Rubinstein E.
Biochim. Biophys. Acta 1478:159-163(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Adrenal gland and Teratocarcinoma.
[4]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT SER-57.
Tissue: Brain.
[7]"Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid precursor protein."
Xu D., Sharma C., Hemler M.E.
FASEB J. 23:3674-3681(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ADAM10, PALMITOYLATION, MUTAGENESIS OF CYS-9; CYS-12 AND CYS-83.
[8]"Tetraspanin proteins regulate membrane type-1 matrix metalloproteinase-dependent pericellular proteolysis."
Lafleur M.A., Xu D., Hemler M.E.
Mol. Biol. Cell 20:2030-2040(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Next-generation sequencing of a 40 Mb linkage interval reveals TSPAN12 mutations in patients with familial exudative vitreoretinopathy."
Nikopoulos K., Gilissen C., Hoischen A., van Nouhuys C.E., Boonstra F.N., Blokland E.A., Arts P., Wieskamp N., Strom T.M., Ayuso C., Tilanus M.A., Bouwhuis S., Mukhopadhyay A., Scheffer H., Hoefsloot L.H., Veltman J.A., Cremers F.P., Collin R.W.
Am. J. Hum. Genet. 86:240-247(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EVR5 ARG-188 AND PRO-237.
[10]"Mutations in TSPAN12 cause autosomal-dominant familial exudative vitreoretinopathy."
Poulter J.A., Ali M., Gilmour D.F., Rice A., Kondo H., Hayashi K., Mackey D.A., Kearns L.S., Ruddle J.B., Craig J.E., Pierce E.A., Downey L.M., Mohamed M.D., Markham A.F., Inglehearn C.F., Toomes C.
Am. J. Hum. Genet. 86:248-253(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EVR5 HIS-101 AND ARG-210.
[11]"Recessive mutations in TSPAN12 cause retinal dysplasia and severe familial exudative vitreoretinopathy (FEVR)."
Poulter J.A., Davidson A.E., Ali M., Gilmour D.F., Parry D.A., Mintz-Hittner H.A., Carr I.M., Bottomley H.M., Long V.W., Downey L.M., Sergouniotis P.I., Wright G.A., MacLaren R.E., Moore A.T., Webster A.R., Inglehearn C.F., Toomes C.
Invest. Ophthalmol. Vis. Sci. 53:2873-2879(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS EVR5 MET-49; CYS-138 AND PRO-223.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS5777.1. [O95859-1]
RefSeqNP_036470.1. NM_012338.3. [O95859-1]
XP_005250296.1. XM_005250239.1. [O95859-1]
UniGeneHs.16529.

3D structure databases

ProteinModelPortalO95859.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117098. 1 interaction.
IntActO95859. 3 interactions.
STRING9606.ENSP00000222747.

PTM databases

PhosphoSiteO95859.

Proteomic databases

PaxDbO95859.
PRIDEO95859.

Protocols and materials databases

DNASU23554.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000222747; ENSP00000222747; ENSG00000106025. [O95859-1]
ENST00000415871; ENSP00000397699; ENSG00000106025. [O95859-1]
GeneID23554.
KEGGhsa:23554.
UCSCuc003vjk.3. human. [O95859-1]

Organism-specific databases

CTD23554.
GeneCardsGC07M120427.
GeneReviewsTSPAN12.
HGNCHGNC:21641. TSPAN12.
HPAHPA051570.
MIM613138. gene.
613310. phenotype.
neXtProtNX_O95859.
Orphanet891. Familial exudative vitreoretinopathy.
PharmGKBPA134954047.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG257008.
HOGENOMHOG000252919.
HOVERGENHBG054253.
InParanoidO95859.
KOK17355.
OMATYEQEIM.
OrthoDBEOG7SFHX2.
PhylomeDBO95859.
TreeFamTF316345.

Gene expression databases

ArrayExpressO95859.
BgeeO95859.
CleanExHS_TSPAN12.
GenevestigatorO95859.

Family and domain databases

InterProIPR000301. Tetraspanin.
IPR018499. Tetraspanin/Peripherin.
IPR018503. Tetraspanin_CS.
IPR008952. Tetraspanin_EC2.
[Graphical view]
PfamPF00335. Tetraspannin. 1 hit.
[Graphical view]
PIRSFPIRSF002419. Tetraspanin. 1 hit.
PRINTSPR00259. TMFOUR.
SUPFAMSSF48652. SSF48652. 1 hit.
PROSITEPS00421. TM4_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTSPAN12.
GenomeRNAi23554.
NextBio46116.
PROO95859.
SOURCESearch...

Entry information

Entry nameTSN12_HUMAN
AccessionPrimary (citable) accession number: O95859
Secondary accession number(s): A4D0V8 expand/collapse secondary AC list , B4DRG6, Q549U9, Q8N5Y0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 1999
Last modified: July 9, 2014
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM