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Q8BKT6

- TSN12_MOUSE

UniProt

Q8BKT6 - TSN12_MOUSE

Protein

Tetraspanin-12

Gene

Tspan12

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 88 (01 Oct 2014)
      Sequence version 1 (01 Mar 2003)
      Previous versions | rss
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    Functioni

    Regulator of cell surface receptor signal transduction. 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 similarity. 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 similarity1 Publication

    GO - Biological processi

    1. angiogenesis Source: UniProtKB-KW
    2. cell surface receptor signaling pathway Source: UniProtKB
    3. regulation of angiogenesis Source: UniProtKB
    4. retina layer formation Source: UniProtKB

    Keywords - Biological processi

    Angiogenesis

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tetraspanin-12
    Short name:
    Tspan-12
    Alternative name(s):
    Transmembrane 4 superfamily member 12
    Gene namesi
    Name:Tspan12
    Synonyms:Tm4sf12
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 6

    Organism-specific databases

    MGIiMGI:1889818. Tspan12.

    Subcellular locationi

    Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. integral component of plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Disruption phenotypei

    Mice are viable and fertile but display defects in retinal vascularization. In retinas between P5 and P12, the centrifugal outgrowth of the nerve fiber layer (NFL) vasculature is moderately delayed in retinas. At P11, vertical sprouts and plexiform layer (OPL) capillaries appear in wild-type mice, whereas both are completely absent in mutant mice. In adult mutant mice, the plexiform layer (OPL) remains avascular, confirming that the defect is not transient. The thickness of the outer nuclear layer in retinas is consistently reduced in adult mutant but not neonatal mice, indicating that neural cells are secondarily affected by the vascular defects.1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 305305Tetraspanin-12PRO_0000290009Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Lipidationi9 – 91S-palmitoyl cysteineBy similarity
    Lipidationi12 – 121S-palmitoyl cysteineBy similarity
    Lipidationi83 – 831S-palmitoyl cysteineBy similarity

    Post-translational modificationi

    Palmitoylated; required for interaction with ADAM10.By similarity

    Keywords - PTMi

    Lipoprotein, Palmitate

    Proteomic databases

    PRIDEiQ8BKT6.

    PTM databases

    PhosphoSiteiQ8BKT6.

    Expressioni

    Tissue specificityi

    Expressed in the neonatal retinal vasculature but not other retinal tissues. Also detected in the neonatal meningeal vasculature and in nonvascular cell types, such as the smooth muscle cells in the neonatal intestine.1 Publication

    Gene expression databases

    BgeeiQ8BKT6.
    CleanExiMM_TSPAN12.
    GenevestigatoriQ8BKT6.

    Interactioni

    Subunit structurei

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

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000031678.

    Structurei

    3D structure databases

    ProteinModelPortaliQ8BKT6.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1212CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini34 – 5926ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini81 – 899CytoplasmicSequence Analysis
    Topological domaini111 – 224114ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini246 – 30560CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei13 – 3321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei60 – 8021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei90 – 11021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei225 – 24521HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the tetraspanin (TM4SF) family.Curated

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG257008.
    GeneTreeiENSGT00510000047764.
    HOGENOMiHOG000252919.
    HOVERGENiHBG054253.
    InParanoidiQ8BKT6.
    KOiK17355.
    OMAiTYEQEIM.
    OrthoDBiEOG7SFHX2.
    PhylomeDBiQ8BKT6.
    TreeFamiTF316345.

    Family and domain databases

    InterProiIPR000301. Tetraspanin.
    IPR018499. Tetraspanin/Peripherin.
    IPR018503. Tetraspanin_CS.
    IPR008952. Tetraspanin_EC2.
    [Graphical view]
    PfamiPF00335. Tetraspannin. 1 hit.
    [Graphical view]
    PIRSFiPIRSF002419. Tetraspanin. 1 hit.
    PRINTSiPR00259. TMFOUR.
    SUPFAMiSSF48652. SSF48652. 1 hit.
    PROSITEiPS00421. TM4_1. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q8BKT6-1) [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

    MAREDSVKCL RCLLYALNLL FWLMSISVLA VSAWMRDYLN NVLTLTAETR    50
    VEEAVILTYF PVVHPVMIAV CCFLIIVGML GYCGTVKRNL LLLAWYFGTL 100
    LVIFCVELAC GVWTYEQEVM VPVQWSDMVT LKARMTNYGL PRYRWLTHAW 150
    NYFQREFKCC GVVYFTDWLE MTEMDWPPDS CCVREFPGCS KQAHQEDLSD 200
    LYQEGCGKKM YSFLRGTKQL QVLRFLGISI GVTQILAMIL TITLLWALYY 250
    DRREPGTDQM LSLKNDTSQH LSCHSVELLK PSLSRIFEHT SMANSFNTHF 300
    EMEEL 305
    Length:305
    Mass (Da):35,408
    Last modified:March 1, 2003 - v1
    Checksum:i1C5C36D37F002F06
    GO
    Isoform 2 (identifier: Q8BKT6-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         156-203: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:257
    Mass (Da):29,757
    Checksum:i63E3157D3EC429C2
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti8 – 81K → E in BAC28354. (PubMed:16141072)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei156 – 20348Missing in isoform 2. 1 PublicationVSP_038526Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK033554 mRNA. Translation: BAC28354.1.
    AK050737 mRNA. Translation: BAC34399.1.
    CH466533 Genomic DNA. Translation: EDL13857.1.
    BC065152 mRNA. Translation: AAH65152.1.
    BC068240 mRNA. Translation: AAH68240.1.
    CCDSiCCDS19935.1. [Q8BKT6-1]
    RefSeqiNP_766595.1. NM_173007.3. [Q8BKT6-1]
    XP_006505153.1. XM_006505090.1. [Q8BKT6-1]
    XP_006505154.1. XM_006505091.1. [Q8BKT6-1]
    UniGeneiMm.21950.

    Genome annotation databases

    EnsembliENSMUST00000031678; ENSMUSP00000031678; ENSMUSG00000029669. [Q8BKT6-1]
    ENSMUST00000120965; ENSMUSP00000113384; ENSMUSG00000029669. [Q8BKT6-2]
    GeneIDi269831.
    KEGGimmu:269831.
    UCSCiuc009bar.1. mouse. [Q8BKT6-1]
    uc012eij.1. mouse. [Q8BKT6-2]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AK033554 mRNA. Translation: BAC28354.1 .
    AK050737 mRNA. Translation: BAC34399.1 .
    CH466533 Genomic DNA. Translation: EDL13857.1 .
    BC065152 mRNA. Translation: AAH65152.1 .
    BC068240 mRNA. Translation: AAH68240.1 .
    CCDSi CCDS19935.1. [Q8BKT6-1 ]
    RefSeqi NP_766595.1. NM_173007.3. [Q8BKT6-1 ]
    XP_006505153.1. XM_006505090.1. [Q8BKT6-1 ]
    XP_006505154.1. XM_006505091.1. [Q8BKT6-1 ]
    UniGenei Mm.21950.

    3D structure databases

    ProteinModelPortali Q8BKT6.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 10090.ENSMUSP00000031678.

    PTM databases

    PhosphoSitei Q8BKT6.

    Proteomic databases

    PRIDEi Q8BKT6.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000031678 ; ENSMUSP00000031678 ; ENSMUSG00000029669 . [Q8BKT6-1 ]
    ENSMUST00000120965 ; ENSMUSP00000113384 ; ENSMUSG00000029669 . [Q8BKT6-2 ]
    GeneIDi 269831.
    KEGGi mmu:269831.
    UCSCi uc009bar.1. mouse. [Q8BKT6-1 ]
    uc012eij.1. mouse. [Q8BKT6-2 ]

    Organism-specific databases

    CTDi 23554.
    MGIi MGI:1889818. Tspan12.

    Phylogenomic databases

    eggNOGi NOG257008.
    GeneTreei ENSGT00510000047764.
    HOGENOMi HOG000252919.
    HOVERGENi HBG054253.
    InParanoidi Q8BKT6.
    KOi K17355.
    OMAi TYEQEIM.
    OrthoDBi EOG7SFHX2.
    PhylomeDBi Q8BKT6.
    TreeFami TF316345.

    Miscellaneous databases

    NextBioi 393053.
    PROi Q8BKT6.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q8BKT6.
    CleanExi MM_TSPAN12.
    Genevestigatori Q8BKT6.

    Family and domain databases

    InterProi IPR000301. Tetraspanin.
    IPR018499. Tetraspanin/Peripherin.
    IPR018503. Tetraspanin_CS.
    IPR008952. Tetraspanin_EC2.
    [Graphical view ]
    Pfami PF00335. Tetraspannin. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF002419. Tetraspanin. 1 hit.
    PRINTSi PR00259. TMFOUR.
    SUPFAMi SSF48652. SSF48652. 1 hit.
    PROSITEi PS00421. TM4_1. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Strain: C57BL/6J.
      Tissue: Colon.
    2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "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] (ISOFORMS 1 AND 2).
      Strain: C57BL/6 and Czech II.
      Tissue: Brain and Mammary tumor.
    4. "TSPAN12 regulates retinal vascular development by promoting Norrin-but not Wnt-induced FZD4/beta-catenin signaling."
      Junge H.J., Yang S., Burton J.B., Paes K., Shu X., French D.M., Costa M., Rice D.S., Ye W.
      Cell 139:299-311(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, IDENTIFICATION IN A COMPLEX WITH FZD4 AND NDP, DISRUPTION PHENOTYPE.

    Entry informationi

    Entry nameiTSN12_MOUSE
    AccessioniPrimary (citable) accession number: Q8BKT6
    Secondary accession number(s): Q6P1C3, Q8BZU1
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: June 12, 2007
    Last sequence update: March 1, 2003
    Last modified: October 1, 2014
    This is version 88 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3