ID   PCD12_MOUSE             Reviewed;        1180 AA.
AC   O55134; G5E847;
DT   02-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT   18-SEP-2013, sequence version 2.
DT   24-JAN-2024, entry version 161.
DE   RecName: Full=Protocadherin-12 {ECO:0000305};
DE   AltName: Full=Vascular cadherin-2 {ECO:0000303|PubMed:9651350};
DE   AltName: Full=Vascular endothelial cadherin-2 {ECO:0000303|PubMed:9651350};
DE            Short=VE-cad-2 {ECO:0000303|PubMed:9651350};
DE            Short=VE-cadherin-2 {ECO:0000303|PubMed:9651350};
DE   Contains:
DE     RecName: Full=Protocadherin-12, secreted form {ECO:0000250|UniProtKB:Q9NPG4};
DE   Flags: Precursor;
GN   Name=Pcdh12 {ECO:0000312|MGI:MGI:1855700};
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 [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Brain capillary;
RX   PubMed=9651350; DOI=10.1074/jbc.273.28.17565;
RA   Telo P., Breviario F., Huber P., Panzeri C., Dejana E.;
RT   "Identification of a novel cadherin (vascular endothelial cadherin-2)
RT   located at intercellular junctions in endothelial cells.";
RL   J. Biol. Chem. 273:17565-17572(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND GLYCOSYLATION.
RX   PubMed=15541725; DOI=10.1016/j.yexcr.2004.08.024;
RA   Rampon C., Prandini M.H., Bouillot S., Pointu H., Tillet E., Frank R.,
RA   Vernet M., Huber P.;
RT   "Protocadherin 12 (VE-cadherin 2) is expressed in endothelial, trophoblast,
RT   and mesangial cells.";
RL   Exp. Cell Res. 302:48-60(2005).
RN   [5]
RP   TISSUE SPECIFICITY.
RX   PubMed=16269175; DOI=10.1016/j.placenta.2005.09.009;
RA   Bouillot S., Rampon C., Tillet E., Huber P.;
RT   "Tracing the glycogen cells with protocadherin 12 during mouse placenta
RT   development.";
RL   Placenta 27:882-888(2006).
RN   [6]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=18477666; DOI=10.1152/physiolgenomics.00220.2007;
RA   Rampon C., Bouillot S., Climescu-Haulica A., Prandini M.H., Cand F.,
RA   Vandenbrouck Y., Huber P.;
RT   "Protocadherin 12 deficiency alters morphogenesis and transcriptional
RT   profile of the placenta.";
RL   Physiol. Genomics 34:193-204(2008).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-859, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Heart, Kidney, Lung, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [8]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=22205043; DOI=10.1016/j.patbio.2011.11.005;
RA   Philibert C., Bouillot S., Huber P., Faury G.;
RT   "Protocadherin-12 deficiency leads to modifications in the structure and
RT   function of arteries in mice.";
RL   Pathol. Biol. 60:34-40(2012).
CC   -!- FUNCTION: Cellular adhesion molecule that may play an important role in
CC       cell-cell interactions at interendothelial junctions (PubMed:9651350).
CC       Acts as a regulator of cell migration, probably via increasing cell-
CC       cell adhesion (By similarity). Promotes homotypic calcium-dependent
CC       aggregation and adhesion and clusters at intercellular junctions
CC       (PubMed:9651350). Unable to bind to catenins, weakly associates with
CC       the cytoskeleton (PubMed:9651350). {ECO:0000250|UniProtKB:Q9NPG4,
CC       ECO:0000269|PubMed:9651350}.
CC   -!- SUBCELLULAR LOCATION: [Protocadherin-12]: Cell membrane
CC       {ECO:0000250|UniProtKB:Q9NPG4}; Single-pass type I membrane protein
CC       {ECO:0000255}. Cell junction {ECO:0000269|PubMed:9651350}.
CC   -!- SUBCELLULAR LOCATION: [Protocadherin-12, secreted form]: Secreted
CC       {ECO:0000250|UniProtKB:Q9NPG4}. Note=The secreted form is produced
CC       following cleavage by ADAM10. {ECO:0000250|UniProtKB:Q9NPG4}.
CC   -!- TISSUE SPECIFICITY: Expressed in endothelial cells: localizes in
CC       vasculogenic rather than angiogenic endothelium (PubMed:9651350,
CC       PubMed:15541725). Strongly expressed in a subset of invasive cells of
CC       the placenta, named glycogen-rich trophoblasts cells (at protein level)
CC       (PubMed:15541725). glycogen-rich trophoblasts cells originate from the
CC       from the ectoplacental cone where they rapidly form tight islets (at
CC       protein level) (PubMed:16269175). In adult mice, present at high level
CC       in mesangial cells of kidney glomeruli, while expression was not
CC       detected in other types of perivascular cells (PubMed:15541725).
CC       {ECO:0000269|PubMed:15541725, ECO:0000269|PubMed:16269175,
CC       ECO:0000269|PubMed:9651350}.
CC   -!- PTM: N-glycosylated. {ECO:0000269|PubMed:15541725}.
CC   -!- PTM: [Protocadherin-12]: Cleaved by ADAM10 close to the transmembrane
CC       domain to release the Protocadherin-12, secreted form in the serum.
CC       Cleavage results in reduced cellular adhesion in a cell migration
CC       assay. {ECO:0000250|UniProtKB:Q9NPG4}.
CC   -!- DISRUPTION PHENOTYPE: Mice are viable and fertile (PubMed:15541725,
CC       PubMed:18477666). Mice however show alterations in placental
CC       development that result in embryonic growth retardation: placentas are
CC       smaller and show limited angiogenesis and mis-segregation of the
CC       labyrinthine and intermediate layers (PubMed:18477666). Mice also
CC       display modifications in the structure and function of arteries, such
CC       as rearrangement of the arterial wall elastic fibers (PubMed:22205043).
CC       {ECO:0000269|PubMed:15541725, ECO:0000269|PubMed:18477666,
CC       ECO:0000269|PubMed:22205043}.
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DR   EMBL; Y08715; CAA69965.1; -; mRNA.
DR   EMBL; AC133646; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC152450; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH466528; EDL10091.1; -; Genomic_DNA.
DR   CCDS; CCDS29199.1; -.
DR   PIR; T31066; T31066.
DR   RefSeq; NP_059074.2; NM_017378.2.
DR   AlphaFoldDB; O55134; -.
DR   SMR; O55134; -.
DR   BioGRID; 207321; 1.
DR   IntAct; O55134; 1.
DR   STRING; 10090.ENSMUSP00000025311; -.
DR   GlyCosmos; O55134; 5 sites, No reported glycans.
DR   GlyGen; O55134; 5 sites.
DR   iPTMnet; O55134; -.
DR   PhosphoSitePlus; O55134; -.
DR   MaxQB; O55134; -.
DR   PaxDb; 10090-ENSMUSP00000025311; -.
DR   ProteomicsDB; 294340; -.
DR   Antibodypedia; 27396; 119 antibodies from 26 providers.
DR   DNASU; 53601; -.
DR   Ensembl; ENSMUST00000025311.8; ENSMUSP00000025311.6; ENSMUSG00000024440.14.
DR   GeneID; 53601; -.
DR   KEGG; mmu:53601; -.
DR   UCSC; uc008esb.1; mouse.
DR   AGR; MGI:1855700; -.
DR   CTD; 51294; -.
DR   MGI; MGI:1855700; Pcdh12.
DR   VEuPathDB; HostDB:ENSMUSG00000024440; -.
DR   eggNOG; KOG3594; Eukaryota.
DR   GeneTree; ENSGT00940000160403; -.
DR   HOGENOM; CLU_006480_1_2_1; -.
DR   InParanoid; O55134; -.
DR   OMA; ALFMSIC; -.
DR   OrthoDB; 4259465at2759; -.
DR   PhylomeDB; O55134; -.
DR   TreeFam; TF352008; -.
DR   BioGRID-ORCS; 53601; 0 hits in 77 CRISPR screens.
DR   ChiTaRS; Pcdh12; mouse.
DR   PRO; PR:O55134; -.
DR   Proteomes; UP000000589; Chromosome 18.
DR   RNAct; O55134; Protein.
DR   Bgee; ENSMUSG00000024440; Expressed in left lung lobe and 134 other cell types or tissues.
DR   ExpressionAtlas; O55134; baseline and differential.
DR   GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; ISS:MGI.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0016339; P:calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; IDA:MGI.
DR   GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR   GO; GO:0005977; P:glycogen metabolic process; IMP:MGI.
DR   GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IDA:MGI.
DR   GO; GO:0060711; P:labyrinthine layer development; IMP:MGI.
DR   CDD; cd11304; Cadherin_repeat; 6.
DR   Gene3D; 2.60.40.60; Cadherins; 6.
DR   InterPro; IPR002126; Cadherin-like_dom.
DR   InterPro; IPR015919; Cadherin-like_sf.
DR   InterPro; IPR020894; Cadherin_CS.
DR   InterPro; IPR013164; Cadherin_N.
DR   PANTHER; PTHR24028; CADHERIN-87A; 1.
DR   PANTHER; PTHR24028:SF42; PROTOCADHERIN-12; 1.
DR   Pfam; PF00028; Cadherin; 4.
DR   Pfam; PF08266; Cadherin_2; 1.
DR   PRINTS; PR00205; CADHERIN.
DR   SMART; SM00112; CA; 6.
DR   SUPFAM; SSF49313; Cadherin-like; 5.
DR   PROSITE; PS00232; CADHERIN_1; 5.
DR   PROSITE; PS50268; CADHERIN_2; 6.
DR   Genevisible; O55134; MM.
PE   1: Evidence at protein level;
KW   Calcium; Cell adhesion; Cell junction; Cell membrane; Glycoprotein;
KW   Membrane; Phosphoprotein; Reference proteome; Repeat; Secreted; Signal;
KW   Transmembrane; Transmembrane helix.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000255"
FT   CHAIN           18..1180
FT                   /note="Protocadherin-12"
FT                   /id="PRO_0000003997"
FT   CHAIN           18..?
FT                   /note="Protocadherin-12, secreted form"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NPG4"
FT                   /id="PRO_0000444042"
FT   TOPO_DOM        18..716
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        717..737
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        738..1180
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          28..135
FT                   /note="Cadherin 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT   DOMAIN          136..244
FT                   /note="Cadherin 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT   DOMAIN          245..352
FT                   /note="Cadherin 3"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT   DOMAIN          355..460
FT                   /note="Cadherin 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT   DOMAIN          461..565
FT                   /note="Cadherin 5"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT   DOMAIN          600..711
FT                   /note="Cadherin 6"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT   REGION          857..930
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          973..1026
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1076..1104
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1156..1180
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        900..920
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1076..1090
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         859
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         1064
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NPG4"
FT   CARBOHYD        265
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        415
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        582
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        659
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        662
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        813
FT                   /note="Q -> E (in Ref. 1; CAA69965)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1180 AA;  128673 MW;  1E2BCC09DFCA4085 CRC64;
     MMLLLPFLLG LLGPGSYLFI SGDCQEVATV MVKFQVTEEV PSGTVIGKLS QELRVEERRG
     KAGDAFQILQ LPQALPVQMN SEDGLLSTSS RLDREKLCRQ EDPCLVSFDV LATGASALIH
     VEIQVLDIND HQPQFPKDEQ ELEISESASL HTRIPLDRAL DQDTGPNSLY SYSLSPSEHF
     ALDVIVGPDE TKHAELVVVK ELDRELHSYF DLVLTAYDNG NPPKSGISVV KVNVLDSNDN
     SPVFAESSLA LEIPEDTVPG TLLINLTATD PDQGPNGEVE FFFGKHVSPE VMNTFGIDAK
     TGQIILRQAL DYEKNPAYEV DVQARDLGPN SIPGHCKVLI KVLDVNDNAP SILITWASQT
     SLVSEDLPRD SFIALVSAND LDSGNNGLVH CWLNQELGHF RLKRTNGNTY MLLTNATLDR
     EQWPIYTLTV FAQDQGPQPL SAEKELQIQV SDVNDNAPVF EKSRYEVSTW ENNPPSLHLI
     TLKAHDADLG SNGKVSYRIK DSPVSHLVII DFETGEVTAQ RSLDYEQMAG FEFQVIAEDR
     GQPQLASSIS VWVSLLDAND NAPEVIQPVL SEGKATLSVL VNASTGHLLL PIENPSGMDP
     AGTGIPPKAT HSPWSFLLLT IVARDADSGA NGELFYSIQS GNDAHLFFLS PSLGQLFINV
     TNASSLIGSQ WDLGIVVEDQ GSPSLQTQVS LKVVFVTSVD HLRDSAHEPG VLSTPALALI
     CLAVLLAIFG LLLALFVSIC RTERKDNRAY NCREAESSYR HQPKRPQKHI QKADIHLVPV
     LRAHENETDE VRPSHKDTSK ETLMEAGWDS CLQAPFHLTP TLYRTLRNQG NQGELAESQE
     VLQDTFNFLF NHPRQRNASR ENLNLPESPP AVRQPLLRPL KVPGSPIARA TGDQDKEEAP
     QSPPASSATL RRQRNFNGKV SPRGESGPHQ ILRSLVRLSV AAFAERNPVE EPAGDSPPVQ
     QISQLLSLLH QGQFQPKPNH RGNKYLAKPG GSSRGTIPDT EGLVGLKPSG QAEPDLEEGP
     PSPEEDLSVK RLLEEELSSL LDPNTGLALD KLSPPDPAWM ARLSLPLTTN YRDNLSSPDA
     TTSEEPRTFQ TFGKTVGPGP ELSPTGTRLA STFVSEMSSL LEMLLGQHTV PVEAASAALR
     RLSVCGRTLS LDLATSGASA SEAQGRKKAA ESRLGCGRNL
//