TSN12_MOUSE
ID TSN12_MOUSE Reviewed; 305 AA.
AC Q8BKT6; Q6P1C3; Q8BZU1;
DT 12-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Tetraspanin-12;
DE Short=Tspan-12;
DE AltName: Full=Transmembrane 4 superfamily member 12;
GN Name=Tspan12; Synonyms=Tm4sf12;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Colon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and Czech II; TISSUE=Brain, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, IDENTIFICATION IN A
RP COMPLEX WITH FZD4 AND NDP, AND DISRUPTION PHENOTYPE.
RX PubMed=19837033; DOI=10.1016/j.cell.2009.07.048;
RA Junge H.J., Yang S., Burton J.B., Paes K., Shu X., French D.M., Costa M.,
RA Rice D.S., Ye W.;
RT "TSPAN12 regulates retinal vascular development by promoting Norrin-but not
RT Wnt-induced FZD4/beta-catenin signaling.";
RL Cell 139:299-311(2009).
CC -!- FUNCTION: Regulator of cell surface receptor signal transduction. Acts
CC as a regulator of membrane proteinases such as ADAM10 and MMP14/MT1-
CC MMP. Activates ADAM10-dependent cleavage activity of amyloid precursor
CC protein (APP). Activates MMP14/MT1-MMP-dependent cleavage activity (By
CC similarity). Plays a central role in retinal vascularization by
CC regulating norrin (NDP) signal transduction. Acts in concert with
CC norrin (NDP) to promote FZD4 multimerization and subsequent activation
CC of FZD4, leading to promote accumulation of beta-catenin (CTNNB1) and
CC stimulate LEF/TCF-mediated transcriptional programs. Suprisingly, it
CC only activate the norrin (NDP)-dependent activation of FZD4, while it
CC does not activate the Wnt-dependent activation of FZD4, suggesting the
CC existence of a Wnt-independent signaling that also promote accumulation
CC the beta-catenin (CTNNB1). {ECO:0000250, ECO:0000269|PubMed:19837033}.
CC -!- SUBUNIT: Interacts (when palmitoylated) with ADAM10. Interacts with
CC MMP14/MT1-MMP (By similarity). Component of a complex, at least
CC composed of TSPAN12, FZD4 and norrin (NDP). {ECO:0000250,
CC ECO:0000269|PubMed:19837033}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:19837033};
CC Multi-pass membrane protein {ECO:0000305|PubMed:19837033}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BKT6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BKT6-2; Sequence=VSP_038526;
CC -!- TISSUE SPECIFICITY: Expressed in the neonatal retinal vasculature but
CC not other retinal tissues. Also detected in the neonatal meningeal
CC vasculature and in nonvascular cell types, such as the smooth muscle
CC cells in the neonatal intestine. {ECO:0000269|PubMed:19837033}.
CC -!- PTM: Palmitoylated; required for interaction with ADAM10.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable and fertile but display defects
CC in retinal vascularization. In retinas between P5 and P12, the
CC centrifugal outgrowth of the nerve fiber layer (NFL) vasculature is
CC moderately delayed in retinas. At P11, vertical sprouts and plexiform
CC layer (OPL) capillaries appear in wild-type mice, whereas both are
CC completely absent in mutant mice. In adult mutant mice, the plexiform
CC layer (OPL) remains avascular, confirming that the defect is not
CC transient. The thickness of the outer nuclear layer in retinas is
CC consistently reduced in adult mutant but not neonatal mice, indicating
CC that neural cells are secondarily affected by the vascular defects.
CC {ECO:0000269|PubMed:19837033}.
CC -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}.
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DR EMBL; AK033554; BAC28354.1; -; mRNA.
DR EMBL; AK050737; BAC34399.1; -; mRNA.
DR EMBL; CH466533; EDL13857.1; -; Genomic_DNA.
DR EMBL; BC065152; AAH65152.1; -; mRNA.
DR EMBL; BC068240; AAH68240.1; -; mRNA.
DR CCDS; CCDS19935.1; -. [Q8BKT6-1]
DR CCDS; CCDS90030.1; -. [Q8BKT6-2]
DR RefSeq; NP_766595.1; NM_173007.3. [Q8BKT6-1]
DR RefSeq; XP_006505153.1; XM_006505090.2. [Q8BKT6-1]
DR RefSeq; XP_006505154.1; XM_006505091.3. [Q8BKT6-1]
DR RefSeq; XP_017177090.1; XM_017321601.1.
DR RefSeq; XP_017177091.1; XM_017321602.1. [Q8BKT6-1]
DR AlphaFoldDB; Q8BKT6; -.
DR STRING; 10090.ENSMUSP00000031678; -.
DR PhosphoSitePlus; Q8BKT6; -.
DR PaxDb; Q8BKT6; -.
DR PRIDE; Q8BKT6; -.
DR Antibodypedia; 31686; 201 antibodies from 29 providers.
DR DNASU; 269831; -.
DR Ensembl; ENSMUST00000031678; ENSMUSP00000031678; ENSMUSG00000029669. [Q8BKT6-1]
DR Ensembl; ENSMUST00000120965; ENSMUSP00000113384; ENSMUSG00000029669. [Q8BKT6-2]
DR GeneID; 269831; -.
DR KEGG; mmu:269831; -.
DR UCSC; uc009bar.1; mouse. [Q8BKT6-1]
DR UCSC; uc012eij.1; mouse. [Q8BKT6-2]
DR CTD; 23554; -.
DR MGI; MGI:1889818; Tspan12.
DR VEuPathDB; HostDB:ENSMUSG00000029669; -.
DR eggNOG; KOG3882; Eukaryota.
DR GeneTree; ENSGT00510000047764; -.
DR InParanoid; Q8BKT6; -.
DR OMA; GCSRSNK; -.
DR OrthoDB; 954168at2759; -.
DR PhylomeDB; Q8BKT6; -.
DR TreeFam; TF316345; -.
DR BioGRID-ORCS; 269831; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Tspan12; mouse.
DR PRO; PR:Q8BKT6; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8BKT6; protein.
DR Bgee; ENSMUSG00000029669; Expressed in brown adipose tissue and 254 other tissues.
DR ExpressionAtlas; Q8BKT6; baseline and differential.
DR Genevisible; Q8BKT6; MM.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:1900746; P:regulation of vascular endothelial growth factor signaling pathway; IBA:GO_Central.
DR GO; GO:0010842; P:retina layer formation; IMP:UniProtKB.
DR Gene3D; 1.10.1450.10; -; 1.
DR InterPro; IPR018499; Tetraspanin/Peripherin.
DR InterPro; IPR000301; Tetraspanin_animals.
DR InterPro; IPR018503; Tetraspanin_CS.
DR InterPro; IPR008952; Tetraspanin_EC2_sf.
DR PANTHER; PTHR19282; PTHR19282; 1.
DR Pfam; PF00335; Tetraspanin; 1.
DR PIRSF; PIRSF002419; Tetraspanin; 1.
DR SUPFAM; SSF48652; SSF48652; 1.
DR PROSITE; PS00421; TM4_1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Angiogenesis; Cell membrane; Lipoprotein; Membrane;
KW Palmitate; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..305
FT /note="Tetraspanin-12"
FT /id="PRO_0000290009"
FT TOPO_DOM 1..12
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 34..59
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 60..80
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..89
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 90..110
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 111..224
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 225..245
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 246..305
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT LIPID 9
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 12
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 83
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 156..203
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038526"
FT CONFLICT 8
FT /note="K -> E (in Ref. 1; BAC28354)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 305 AA; 35408 MW; 1C5C36D37F002F06 CRC64;
MAREDSVKCL RCLLYALNLL FWLMSISVLA VSAWMRDYLN NVLTLTAETR VEEAVILTYF
PVVHPVMIAV CCFLIIVGML GYCGTVKRNL LLLAWYFGTL LVIFCVELAC GVWTYEQEVM
VPVQWSDMVT LKARMTNYGL PRYRWLTHAW NYFQREFKCC GVVYFTDWLE MTEMDWPPDS
CCVREFPGCS KQAHQEDLSD LYQEGCGKKM YSFLRGTKQL QVLRFLGISI GVTQILAMIL
TITLLWALYY DRREPGTDQM LSLKNDTSQH LSCHSVELLK PSLSRIFEHT SMANSFNTHF
EMEEL
