PCD12_MOUSE
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 03-AUG-2022, entry version 154.
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 GlyGen; O55134; 5 sites.
DR iPTMnet; O55134; -.
DR PhosphoSitePlus; O55134; -.
DR MaxQB; O55134; -.
DR PaxDb; O55134; -.
DR PRIDE; O55134; -.
DR ProteomicsDB; 294340; -.
DR Antibodypedia; 27396; 89 antibodies from 26 providers.
DR DNASU; 53601; -.
DR Ensembl; ENSMUST00000025311; ENSMUSP00000025311; ENSMUSG00000024440.
DR GeneID; 53601; -.
DR KEGG; mmu:53601; -.
DR UCSC; uc008esb.1; mouse.
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; REQWPKY; -.
DR OrthoDB; 64478at2759; -.
DR PhylomeDB; O55134; -.
DR TreeFam; TF352008; -.
DR BioGRID-ORCS; 53601; 0 hits in 72 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 133 other tissues.
DR ExpressionAtlas; O55134; baseline and differential.
DR Genevisible; O55134; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of 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 InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR020894; Cadherin_CS.
DR InterPro; IPR013164; Cadherin_N.
DR InterPro; IPR030720; Protocadherin-12.
DR PANTHER; PTHR24028:SF42; PTHR24028:SF42; 1.
DR Pfam; PF00028; Cadherin; 4.
DR Pfam; PF08266; Cadherin_2; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 6.
DR SUPFAM; SSF49313; SSF49313; 5.
DR PROSITE; PS00232; CADHERIN_1; 5.
DR PROSITE; PS50268; CADHERIN_2; 6.
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
