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   24-JAN-2024, entry version 84.
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 17 dpc, 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. [D3ZE55-2]
DR   RefSeq; XP_008769119.1; XM_008770897.2.
DR   AlphaFoldDB; D3ZE55; -.
DR   SMR; D3ZE55; -.
DR   STRING; 10116.ENSRNOP00000017599; -.
DR   GlyCosmos; D3ZE55; 2 sites, 4 glycans.
DR   GlyGen; D3ZE55; 2 sites, 4 N-linked glycans (1 site).
DR   iPTMnet; D3ZE55; -.
DR   PhosphoSitePlus; D3ZE55; -.
DR   SwissPalm; D3ZE55; -.
DR   PaxDb; 10116-ENSRNOP00000017599; -.
DR   Ensembl; ENSRNOT00000017599.4; ENSRNOP00000017599.3; ENSRNOG00000013101.4. [D3ZE55-1]
DR   GeneID; 64865; -.
DR   KEGG; rno:64865; -.
DR   AGR; RGD:69350; -.
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; 4259465at2759; -.
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 cell types or tissues.
DR   GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR   GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR   GO; GO:0045211; C:postsynaptic membrane; IDA:SynGO.
DR   GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA: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; IDA: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   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:SF46; PROTOCADHERIN-8; 1.
DR   Pfam; PF00028; Cadherin; 5.
DR   Pfam; PF08266; Cadherin_2; 1.
DR   PRINTS; PR00205; CADHERIN.
DR   SMART; SM00112; CA; 6.
DR   SUPFAM; SSF49313; Cadherin-like; 6.
DR   PROSITE; PS00232; CADHERIN_1; 5.
DR   PROSITE; PS50268; CADHERIN_2; 6.
DR   Genevisible; D3ZE55; RN.
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
//