ID PCDH8_HUMAN Reviewed; 1070 AA. AC O95206; B4DMV7; Q5TAN1; Q5TAN2; Q8IYE9; Q96SF1; DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 2. DT 13-FEB-2019, entry version 161. DE RecName: Full=Protocadherin-8; DE AltName: Full=Arcadlin; DE Flags: Precursor; GN Name=PCDH8; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9787079; DOI=10.1006/geno.1998.5467; RA Strehl S., Glatt K., Liu Q.M., Glatt H., Lalande M.; RT "Characterization of two novel protocadherins (PCDH8 and PCDH9) RT localized on human chromosome 13 and mouse chromosome 14."; RL Genomics 53:81-89(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=11230163; DOI=10.1101/gr.167301; RA Wu Q., Zhang T., Cheng J.-F., Kim Y., Grimwood J., Schmutz J., RA Dickson M., Noonan J.P., Zhang M.Q., Myers R.M., Maniatis T.; RT "Comparative DNA sequence analysis of mouse and human protocadherin RT gene clusters."; RL Genome Res. 11:389-404(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T., RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., RA Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., RA Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP VARIANTS ARG-7; ALA-39 AND ALA-743. RX PubMed=12884975; DOI=10.1034/j.1601-183X.2002.10307.x; RA Bray N.J., Kirov G., Owen R.J., Jacobsen N.J., Georgieva L., RA Williams H.J., Norton N., Spurlock G., Jones S., Zammit S., RA O'Donovan M.C., Owen M.J.; RT "Screening the human protocadherin 8 (PCDH8) gene in schizophrenia."; RL Genes Brain Behav. 1:187-191(2002). RN [8] RP VARIANT [LARGE SCALE ANALYSIS] ASN-956. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Calcium-dependent cell-adhesion protein (By similarity). CC May play a role in activity-induced synaptic reorganization CC underlying long term memory (By similarity). Could be involved in CC CDH2 internalization through TAOK2/p38 MAPK pathway. In CC hippocampal neurons, may play a role in the down-regulation of CC dendritic spines, maybe through its action on CDH2 endocytosis (By CC similarity). {ECO:0000250}. 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 CC lead to CDH2 cointernalization. Interacts with CDH11. Interacts CC with TAOK2. {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass CC type I membrane protein {ECO:0000250}. Cell projection, dendrite CC {ECO:0000250}. Cell junction, synapse, presynaptic cell membrane. CC Cell junction, synapse, postsynaptic cell membrane. Note=Also CC expressed in neuronal cell bodies. Localized to excitatory, but CC not with inhibitory, synapses. {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O95206-1; Sequence=Displayed; CC Name=2; CC IsoId=O95206-2; Sequence=VSP_008706; CC -!- SEQUENCE CAUTION: CC Sequence=BAG60019.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305}; 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; AF061573; AAC70009.2; -; mRNA. DR EMBL; AY013873; AAK21986.1; -; mRNA. DR EMBL; AL139085; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471124; EAW52049.1; -; Genomic_DNA. DR EMBL; CH471124; EAW52050.1; -; Genomic_DNA. DR EMBL; BC036025; AAH36025.1; -; mRNA. DR EMBL; AK297652; BAG60019.1; ALT_SEQ; mRNA. DR CCDS; CCDS9438.1; -. [O95206-1] DR CCDS; CCDS9439.1; -. [O95206-2] DR RefSeq; NP_002581.2; NM_002590.3. [O95206-1] DR RefSeq; NP_116567.1; NM_032949.2. [O95206-2] DR UniGene; Hs.19492; -. DR ProteinModelPortal; O95206; -. DR SMR; O95206; -. DR BioGrid; 111133; 2. DR IntAct; O95206; 3. DR MINT; O95206; -. DR STRING; 9606.ENSP00000367177; -. DR iPTMnet; O95206; -. DR PhosphoSitePlus; O95206; -. DR BioMuta; PCDH8; -. DR PaxDb; O95206; -. DR PeptideAtlas; O95206; -. DR PRIDE; O95206; -. DR ProteomicsDB; 50714; -. DR ProteomicsDB; 50715; -. [O95206-2] DR DNASU; 5100; -. DR Ensembl; ENST00000338862; ENSP00000341350; ENSG00000136099. [O95206-2] DR Ensembl; ENST00000377942; ENSP00000367177; ENSG00000136099. [O95206-1] DR GeneID; 5100; -. DR KEGG; hsa:5100; -. DR UCSC; uc001vhi.4; human. [O95206-1] DR CTD; 5100; -. DR DisGeNET; 5100; -. DR EuPathDB; HostDB:ENSG00000136099.13; -. DR GeneCards; PCDH8; -. DR HGNC; HGNC:8660; PCDH8. DR HPA; HPA010509; -. DR MIM; 603580; gene. DR neXtProt; NX_O95206; -. DR OpenTargets; ENSG00000136099; -. DR PharmGKB; PA33007; -. DR eggNOG; KOG3594; Eukaryota. DR eggNOG; ENOG410XQHI; LUCA. DR GeneTree; ENSGT00940000155219; -. DR HOGENOM; HOG000220892; -. DR HOVERGEN; HBG054878; -. DR InParanoid; O95206; -. DR KO; K16499; -. DR OMA; GPALQWD; -. DR OrthoDB; 64478at2759; -. DR PhylomeDB; O95206; -. DR TreeFam; TF352008; -. DR GeneWiki; PCDH8; -. DR GenomeRNAi; 5100; -. DR PRO; PR:O95206; -. DR Proteomes; UP000005640; Chromosome 13. DR Bgee; ENSG00000136099; Expressed in 102 organ(s), highest expression level in Ammon's horn. DR ExpressionAtlas; O95206; baseline and differential. DR Genevisible; O95206; HS. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central. DR GO; GO:0099055; C:integral component of postsynaptic membrane; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc. DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0007268; P:chemical synaptic transmission; IEA:Ensembl. DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro. DR GO; GO:0016331; P:morphogenesis of embryonic epithelium; IEA:Ensembl. DR GO; GO:0099179; P:regulation of synaptic membrane adhesion; IEA:Ensembl. DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl. 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 2: Evidence at transcript level; KW Alternative splicing; Calcium; Cell adhesion; Cell junction; KW Cell membrane; Cell projection; Complete proteome; Glycoprotein; KW Membrane; Phosphoprotein; Polymorphism; Postsynaptic cell membrane; KW Reference proteome; Repeat; Signal; Synapse; Transmembrane; KW Transmembrane helix. FT SIGNAL 1 29 {ECO:0000255}. FT CHAIN 30 1070 Protocadherin-8. FT /FTId=PRO_0000003993. FT TOPO_DOM 30 749 Extracellular. {ECO:0000255}. FT TRANSMEM 750 770 Helical. {ECO:0000255}. FT TOPO_DOM 771 1070 Cytoplasmic. {ECO:0000255}. FT DOMAIN 30 135 Cadherin 1. {ECO:0000255|PROSITE- FT ProRule:PRU00043}. FT DOMAIN 136 245 Cadherin 2. {ECO:0000255|PROSITE- FT ProRule:PRU00043}. FT DOMAIN 247 354 Cadherin 3. {ECO:0000255|PROSITE- FT ProRule:PRU00043}. FT DOMAIN 393 497 Cadherin 4. {ECO:0000255|PROSITE- FT ProRule:PRU00043}. FT DOMAIN 498 609 Cadherin 5. {ECO:0000255|PROSITE- FT ProRule:PRU00043}. FT DOMAIN 615 723 Cadherin 6. {ECO:0000255|PROSITE- FT ProRule:PRU00043}. FT MOD_RES 1054 1054 Phosphoserine. FT {ECO:0000250|UniProtKB:D3ZE55}. FT CARBOHYD 70 70 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 464 464 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 616 616 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT VAR_SEQ 780 876 Missing (in isoform 2). FT {ECO:0000303|PubMed:11230163}. FT /FTId=VSP_008706. FT VARIANT 7 7 W -> R (in dbSNP:rs3742301). FT {ECO:0000269|PubMed:12884975}. FT /FTId=VAR_017171. FT VARIANT 39 39 E -> A (in dbSNP:rs5030683). FT {ECO:0000269|PubMed:12884975}. FT /FTId=VAR_017172. FT VARIANT 367 367 T -> A (in dbSNP:rs9596693). FT /FTId=VAR_059191. FT VARIANT 743 743 V -> A (in dbSNP:rs5030685). FT {ECO:0000269|PubMed:12884975}. FT /FTId=VAR_017173. FT VARIANT 956 956 K -> N (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_036108. FT CONFLICT 39 39 E -> K (in Ref. 2; AAK21986). FT {ECO:0000305}. FT CONFLICT 834 834 S -> C (in Ref. 5; AAH36025). FT {ECO:0000305}. SQ SEQUENCE 1070 AA; 113019 MW; CBCCE3C43C0E02D8 CRC64; MSPVRRWGSP CLFPLQLFSL CWVLSVAQSK TVRYSTFEED APGTVIGTLA EDLHMKVSGD TSFRLMKQFN SSLLRVREGD GQLTVGDAGL DRERLCGQAP QCVLAFDVVS FSQEQFRLVH VEVEVRDVND HAPRFPRAQI PVEVSEGAAV GTRIPLEVPV DEDVGANGLQ TVRLAEPHSP FRVELQTRAD GAQCADLVLL QELDRESQAA YSLELVAQDG GRPPRSATAA LSVRVLDAND HSPAFPQGAV AEVELAEDAP VGSLLLDLDA ADPDEGPNGD VVFAFGARTP PEARRLFRLD PRSGRLTLAG PVDYERQDTY ELDVRAQDRG PGPRAATCKV IVRIRDVNDN APDIAITPLA APGAPATSPF AAAAAAAALG GADASSPAGA GTPEAGATSL VPEGAARESL VALVSTSDRD SGANGQVRCA LYGHEHFRLQ PAYAGSYLVV TAASLDRERI AEYNLTLVAE DRGAPPLRTV RPYTVRVGDE NDNAPLFTRP VYEVSVRENN PPGAYLATVA ARDRDLGRNG QVTYRLLEAE VGRAGGAVST YVSVDPATGA IYALRSFDYE TLRQLDVRIQ ASDGGSPQLS SSALVQVRVL DQNDHAPVLV HPAPANGSLE VAVPGRTAKD TVVARVQARD ADEGANGELA FELQQQEPRE AFAIGRRTGE ILLTGDLSQE PPGRVFRALL VISDGGRPPL TTTATVSFVV TAGGGRGPAA PASAGSPERS RPPGSRLGVS GSVLQWDTPL IVIIVLAGSC TLLLAAIIAI ATTCNRRKKE VRKGGALREE RPGAAGGGAS APGSPEEAAR GAGPRPNMFD VLTFPGTGKA PFGSPAADAP PPAVAAAEVP GSEGGSATGE SACHFEGQQR LRGAHAEPYG ASPGFGKEPA PPVAVWKGHS FNTISGREAE KFSGKDSGKG DSDFNDSDSD ISGDALKKDL INHMQSGLWA CTAECKILGH SDRCWSPSCS GPNAHPSPHP PAQMSTFCKS TSLPRDPLRR DNYYQAQLPK TVGLQSVYEK VLHRDYDRTV TLLSPPRPGR LPDLQEIGVP LYQSPPGRYL SPKKGANENV //