ID   TSN12_PONAB             Reviewed;         305 AA.
AC   Q5R8B5;
DT   12-JUN-2007, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   03-AUG-2022, entry version 63.
DE   RecName: Full=Tetraspanin-12;
DE            Short=Tspan-12;
GN   Name=TSPAN12;
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Regulator of cell surface receptor signal transduction. Plays
CC       a central role in retinal vascularization by regulating norrin (NDP)
CC       signal transduction. Acts in concert with norrin (NDP) to promote FZD4
CC       multimerization and subsequent activation of FZD4, leading to promote
CC       accumulation of beta-catenin (CTNNB1) and stimulate LEF/TCF-mediated
CC       transcriptional programs. Suprisingly, it only activate the norrin
CC       (NDP)-dependent activation of FZD4, while it does not activate the Wnt-
CC       dependent activation of FZD4, suggesting the existence of a Wnt-
CC       independent signaling that also promote accumulation the beta-catenin
CC       (CTNNB1). Acts as a regulator of membrane proteinases such as ADAM10
CC       and MMP14/MT1-MMP. Activates ADAM10-dependent cleavage activity of
CC       amyloid precursor protein (APP). Activates MMP14/MT1-MMP-dependent
CC       cleavage activity (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Component of a complex, at least composed of TSPAN12, FZD4 and
CC       norrin (NDP) (By similarity). Interacts (when palmitoylated) with
CC       ADAM10. Interacts with MMP14/MT1-MMP (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC       protein {ECO:0000250}.
CC   -!- PTM: Palmitoylated; required for interaction with ADAM10. The precise
CC       position of palmitoylated residues is unclear and occurs either on Cys-
CC       9, Cys-12 and/or Cys-83 (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the tetraspanin (TM4SF) family. {ECO:0000305}.
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DR   EMBL; CR859838; CAH91995.1; -; mRNA.
DR   RefSeq; NP_001127493.1; NM_001134021.1.
DR   AlphaFoldDB; Q5R8B5; -.
DR   STRING; 9601.ENSPPYP00000020123; -.
DR   Ensembl; ENSPPYT00000020915; ENSPPYP00000020123; ENSPPYG00000017944.
DR   GeneID; 100174568; -.
DR   KEGG; pon:100174568; -.
DR   CTD; 23554; -.
DR   eggNOG; KOG3882; Eukaryota.
DR   GeneTree; ENSGT00510000047764; -.
DR   InParanoid; Q5R8B5; -.
DR   OrthoDB; 954168at2759; -.
DR   Proteomes; UP000001595; Chromosome 7.
DR   GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0007166; P:cell surface receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB.
DR   GO; GO:0010842; P:retina layer formation; ISS: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   2: Evidence at transcript level;
KW   Angiogenesis; Cell membrane; Lipoprotein; Membrane; Palmitate;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..305
FT                   /note="Tetraspanin-12"
FT                   /id="PRO_0000290010"
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"
SQ   SEQUENCE   305 AA;  35383 MW;  EBF4D5E1371E92DC CRC64;
     MAREDSVKCL RCLLYALNLL FWLMSISVLA VSAWMRDYLN NVLTLTAETR VEEAVILTYF
     PVVHPVMIAV CCFLIIVGML GYCGTVKRNL LLLAWYFGSL LVIFCVELAC GVWTYEQELM
     VPVQWSDMVT LKARMTNYGL PRYRWLTHAW NFFQREFKCC GVVYFTDWLE MTEMDWPPDS
     CCVREFPGCS KQAHQEDLSD LYQEGCGKKM YSFLRGTKQL QVLRFLGISI GVTQILAMIL
     TITLLWALYY DRREPGTDQM MSLKNDNSQH LSCPSVELLK PSLSRIFEHT SMANSFNTHF
     EMEEL