PCDH8_RAT
ID PCDH8_RAT Reviewed; 1069 AA.
AC D3ZE55; A1A5N4; Q9WVR2;
DT 08-FEB-2011, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 2.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Protocadherin-8;
DE AltName: Full=Activity-regulated cadherin-like protein;
DE Short=Arcadlin;
DE Flags: Precursor;
GN Name=Pcdh8;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBUNIT, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND INDUCTION.
RC TISSUE=Hippocampus;
RX PubMed=10383464; DOI=10.1074/jbc.274.27.19473;
RA Yamagata K., Andreasson K.I., Sugiura H., Maru E., Dominique M., Irie Y.,
RA Miki N., Hayashi Y., Yoshioka M., Kaneko K., Kato H., Worley P.F.;
RT "Arcadlin is a neural activity-regulated cadherin involved in long term
RT potentiation.";
RL J. Biol. Chem. 274:19473-19479(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-694.
RC STRAIN=Brown Norway/NHsdMcwi; TISSUE=Embryonic brain;
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, INTERACTION WITH CDH2; CDH11 AND TAOK2, AND INDUCTION.
RX PubMed=17988630; DOI=10.1016/j.neuron.2007.08.020;
RA Yasuda S., Tanaka H., Sugiura H., Okamura K., Sakaguchi T., Tran U.,
RA Takemiya T., Mizoguchi A., Yagita Y., Sakurai T., De Robertis E.M.,
RA Yamagata K.;
RT "Activity-induced protocadherin arcadlin regulates dendritic spine number
RT by triggering N-cadherin endocytosis via TAO2beta and p38 MAP kinases.";
RL Neuron 56:456-471(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1052, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Calcium-dependent cell-adhesion protein. May play a role in
CC activity-induced synaptic reorganization underlying long term memory.
CC Could be involved in CDH2 internalization through TAOK2/p38 MAPK
CC pathway. In hippocampal neurons, may play a role in the down-regulation
CC of dendritic spines, maybe through its action on CDH2 endocytosis.
CC {ECO:0000269|PubMed:10383464, ECO:0000269|PubMed:17988630}.
CC -!- SUBUNIT: The N-terminal extracellular domain forms homophilic
CC interactions; these interactions activate p38 MAPK via TAOK2 and
CC trigger endocytosis. Interacts with CDH2; this interaction may lead to
CC CDH2 cointernalization. Interacts with CDH11. Interacts with TAOK2.
CC {ECO:0000269|PubMed:10383464, ECO:0000269|PubMed:17988630}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I
CC membrane protein {ECO:0000250}. Cell projection, dendrite
CC {ECO:0000269|PubMed:10383464}. Presynaptic cell membrane
CC {ECO:0000269|PubMed:10383464}. Postsynaptic cell membrane
CC {ECO:0000269|PubMed:10383464}. Note=Also expressed in the cell bodies
CC of neurons of the hippocampus and cortex. Localized to excitatory, but
CC not with inhibitory, synapses.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=D3ZE55-1; Sequence=Displayed;
CC Name=2;
CC IsoId=D3ZE55-2; Sequence=VSP_040565;
CC -!- TISSUE SPECIFICITY: Enriched in brain relative to peripheral tissues,
CC with low expression in the testis. Expressed in hippocampal neurons (at
CC protein level). {ECO:0000269|PubMed:10383464}.
CC -!- DEVELOPMENTAL STAGE: At E17, expressed in the auditory circuit, most
CC prominently in the inferior colliculus, and later in the medial
CC geniculate and the auditory cortex at P0. At P0, also expressed in
CC targets of retinal projections, such as the superior colliculus, the
CC suprachiasmatic nucleus, and the ventrolateral geniculate nucleus. At
CC the same stage, detected in selected structures of the limbic circuit,
CC including the anterior limbic thalamic nuclei, the hippocampus,
CC amygdala and habenula. {ECO:0000269|PubMed:10383464}.
CC -!- INDUCTION: Rapidly and transiently induced by maximal electroconvulsive
CC seizure in the hippocampal granule cells, and modestly induced in the
CC pyramidal cells. Also induced by cAMP. {ECO:0000269|PubMed:10383464,
CC ECO:0000269|PubMed:17988630}.
CC -!- MISCELLANEOUS: [Isoform 2]: May be the only physiologically relevant
CC isoform. {ECO:0000305|PubMed:10383464}.
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DR EMBL; AB026154; BAA82442.1; -; mRNA.
DR EMBL; CH473951; EDM02373.1; -; Genomic_DNA.
DR EMBL; BC128737; AAI28738.1; -; mRNA.
DR RefSeq; NP_074059.1; NM_022868.1.
DR RefSeq; XP_008769119.1; XM_008770897.2. [D3ZE55-1]
DR AlphaFoldDB; D3ZE55; -.
DR SMR; D3ZE55; -.
DR STRING; 10116.ENSRNOP00000017599; -.
DR GlyGen; D3ZE55; 2 sites, 4 N-linked glycans (1 site).
DR iPTMnet; D3ZE55; -.
DR PhosphoSitePlus; D3ZE55; -.
DR SwissPalm; D3ZE55; -.
DR PaxDb; D3ZE55; -.
DR PRIDE; D3ZE55; -.
DR Ensembl; ENSRNOT00000017599; ENSRNOP00000017599; ENSRNOG00000013101. [D3ZE55-1]
DR GeneID; 64865; -.
DR KEGG; rno:64865; -.
DR CTD; 5100; -.
DR RGD; 69350; Pcdh8.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT00940000155219; -.
DR HOGENOM; CLU_006480_1_2_1; -.
DR InParanoid; D3ZE55; -.
DR OMA; GESSCHF; -.
DR OrthoDB; 64478at2759; -.
DR PhylomeDB; D3ZE55; -.
DR PRO; PR:D3ZE55; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Proteomes; UP000234681; Chromosome 15.
DR Bgee; ENSRNOG00000013101; Expressed in frontal cortex and 2 other tissues.
DR Genevisible; D3ZE55; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0099055; C:integral component of postsynaptic membrane; IDA:SynGO.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; EXP:SynGO.
DR GO; GO:0045202; C:synapse; IDA:SynGO.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IDA:RGD.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro.
DR GO; GO:0007616; P:long-term memory; TAS:RGD.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; EXP:SynGO.
DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; ISO:RGD.
DR GO; GO:0099179; P:regulation of synaptic membrane adhesion; IDA:SynGO.
DR GO; GO:0001756; P:somitogenesis; ISO:RGD.
DR InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR020894; Cadherin_CS.
DR InterPro; IPR013164; Cadherin_N.
DR InterPro; IPR030711; Protocadherin-8.
DR PANTHER; PTHR24028:SF46; PTHR24028:SF46; 1.
DR Pfam; PF00028; Cadherin; 5.
DR Pfam; PF08266; Cadherin_2; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 6.
DR SUPFAM; SSF49313; SSF49313; 6.
DR PROSITE; PS00232; CADHERIN_1; 5.
DR PROSITE; PS50268; CADHERIN_2; 6.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell adhesion; Cell membrane;
KW Cell projection; Glycoprotein; Membrane; Phosphoprotein;
KW Postsynaptic cell membrane; Reference proteome; Repeat; Signal; Synapse;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..1069
FT /note="Protocadherin-8"
FT /id="PRO_0000404297"
FT TOPO_DOM 30..747
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 748..768
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 769..1069
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 30..135
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 136..245
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 247..354
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 393..497
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 498..609
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 615..721
FT /note="Cadherin 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REGION 719..738
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 777..859
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 905..927
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1031..1069
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 907..927
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1052
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CARBOHYD 616
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 779..875
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10383464"
FT /id="VSP_040565"
FT CONFLICT 351
FT /note="A -> P (in Ref. 1; BAA82442)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1069 AA; 113191 MW; 307DB9763F69D7D3 CRC64;
MSPVKRWGSP CLFPLQLFSL CWVLSVAQSK TVRYSTFEED APGTVIGTLA EDLHMKVSGD
TSFRLMKQFN SSLLRVREGD GQLTVGDAGL DRERLCGQSP QCVLAFDVVS FSQEQFRLVH
VEVEVRDVND HAPRFPRAQI PVEVSESAPV GTRIPLEVPV DEDVGANGLQ SVRLAEPHSP
FRVELQTRAD GAQCADLVLL QELDRESQAS YSLELVAQDG GRPPRSATAA LSVRVLDAND
HSPAFPQGAV AEVELAEDAP VGSLLLDLDA ADPDEGPNGD VVFTFGARTP PEARHLFRLD
PRSGRLTLAG QVDYERQDTY ELDVRAQDRG PGPRTATCKV IVRIRDVNDN APDISITPLA
APGAPATSPF AAAAAAAALG GADAASSAGS GTQETGVTSL VPEGAARESL VALVSTSDRD
SGANGQVRCA LYGHEHFRLQ PAYAGSYLVV TAASLDRERI AEYNLTLVAE DRGAPPLRTV
RPYTVRVGDE NDNAPLFTKP VYEVSVRENN PPGAYLATVA ARDPDLGRNG QVTYRLVEAE
VGRSGEAVST YVSVDPATGA IYALRSFDYE TLRQLDVRVQ ASDGGSPQLS SNALVQVRVL
DQNDHSPVLV HPAPANGSLE VAVPGRSTKD TAVARIQARD ADEGANGELA FDLLQQEPRE
AFSIGRHTGE IVLTGDLSQE PPGRVFKALL VISDGGRPPL TTTATVSFVV TAGGGSAVPA
SAGSPEHFRP PGSRLAPSGP SLQWDTPLIV IIVLAGSCTL LLAAIIAIAT TCNRRKKEVR
KGGALREERP GAAGGGASAP GSPDETARGT GPRPNMFDVL TFPGSGKAPF GSPAADAPPP
AVAAAEVPGS EGGSATGESA CHFEGQQRLR GAHAEPYSAS PGFGKEPAPP VAVWKGHSFN
TISGREAEKF SGKDSGKGDS DFNDSDSDIS GDALKKDLIN HMQSGLWACT AECKILGHSD
RCWSPSCAGP NTHPPPHPPA QMSTFCKSTS LPRDPLRRDN YYQAQLPKTV GLQSVYEKVL
HRDYDRTVTL LSPPRPGRLP DLQEIGVPLY ESPPGGRYVS PKKGTNENV
