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Protein

Protocadherin-8

Gene

PCDH8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Calcium-dependent cell-adhesion protein (By similarity). May play a role in activity-induced synaptic reorganization underlying long term memory (By similarity). Could be involved in CDH2 internalization through TAOK2/p38 MAPK pathway. In hippocampal neurons, may play a role in the down-regulation of dendritic spines, maybe through its action on CDH2 endocytosis (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Calcium

Names & Taxonomyi

Protein namesi
Recommended name:
Protocadherin-8
Alternative name(s):
Arcadlin
Gene namesi
Name:PCDH8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:8660. PCDH8.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini30 – 749ExtracellularSequence analysisAdd BLAST720
Transmembranei750 – 770HelicalSequence analysisAdd BLAST21
Topological domaini771 – 1070CytoplasmicSequence analysisAdd BLAST300

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • dendrite Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: ProtInc
  • postsynaptic membrane Source: UniProtKB-SubCell
  • presynaptic membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Organism-specific databases

DisGeNETi5100.
OpenTargetsiENSG00000136099.
PharmGKBiPA33007.

Polymorphism and mutation databases

BioMutaiPCDH8.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
ChainiPRO_000000399330 – 1070Protocadherin-8Add BLAST1041

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi70N-linked (GlcNAc...)Sequence analysis1
Glycosylationi464N-linked (GlcNAc...)Sequence analysis1
Glycosylationi616N-linked (GlcNAc...)Sequence analysis1
Modified residuei1054PhosphoserineBy similarity1

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiO95206.
PeptideAtlasiO95206.
PRIDEiO95206.

PTM databases

iPTMnetiO95206.
PhosphoSitePlusiO95206.

Expressioni

Gene expression databases

BgeeiENSG00000136099.
CleanExiHS_PCDH8.
ExpressionAtlasiO95206. baseline and differential.
GenevisibleiO95206. HS.

Organism-specific databases

HPAiHPA010509.

Interactioni

Subunit structurei

The N-terminal extracellular domain forms homophilic interactions; these interactions activate p38 MAPK via TAOK2 and trigger endocytosis. Interacts with CDH2; this interaction may lead to CDH2 cointernalization. Interacts with CDH11. Interacts with TAOK2.By similarity

Protein-protein interaction databases

BioGridi111133. 2 interactors.
IntActiO95206. 3 interactors.
MINTiMINT-2861561.
STRINGi9606.ENSP00000367177.

Structurei

3D structure databases

ProteinModelPortaliO95206.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 135Cadherin 1PROSITE-ProRule annotationAdd BLAST106
Domaini136 – 245Cadherin 2PROSITE-ProRule annotationAdd BLAST110
Domaini247 – 354Cadherin 3PROSITE-ProRule annotationAdd BLAST108
Domaini393 – 497Cadherin 4PROSITE-ProRule annotationAdd BLAST105
Domaini498 – 609Cadherin 5PROSITE-ProRule annotationAdd BLAST112
Domaini615 – 723Cadherin 6PROSITE-ProRule annotationAdd BLAST109

Sequence similaritiesi

Contains 6 cadherin domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3594. Eukaryota.
ENOG410XQHI. LUCA.
GeneTreeiENSGT00850000132246.
HOGENOMiHOG000220892.
HOVERGENiHBG054878.
InParanoidiO95206.
KOiK16499.
OMAiCLIAFDV.
OrthoDBiEOG091G00QD.
PhylomeDBiO95206.
TreeFamiTF352008.

Family and domain databases

Gene3Di2.60.40.60. 6 hits.
InterProiIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR020894. Cadherin_CS.
IPR013164. Cadherin_N.
IPR030711. Protocadherin-8.
[Graphical view]
PANTHERiPTHR24028:SF46. PTHR24028:SF46. 2 hits.
PfamiPF00028. Cadherin. 5 hits.
PF08266. Cadherin_2. 1 hit.
[Graphical view]
PRINTSiPR00205. CADHERIN.
SMARTiSM00112. CA. 6 hits.
[Graphical view]
SUPFAMiSSF49313. SSF49313. 6 hits.
PROSITEiPS00232. CADHERIN_1. 5 hits.
PS50268. CADHERIN_2. 6 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95206-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSPVRRWGSP CLFPLQLFSL CWVLSVAQSK TVRYSTFEED APGTVIGTLA
60 70 80 90 100
EDLHMKVSGD TSFRLMKQFN SSLLRVREGD GQLTVGDAGL DRERLCGQAP
110 120 130 140 150
QCVLAFDVVS FSQEQFRLVH VEVEVRDVND HAPRFPRAQI PVEVSEGAAV
160 170 180 190 200
GTRIPLEVPV DEDVGANGLQ TVRLAEPHSP FRVELQTRAD GAQCADLVLL
210 220 230 240 250
QELDRESQAA YSLELVAQDG GRPPRSATAA LSVRVLDAND HSPAFPQGAV
260 270 280 290 300
AEVELAEDAP VGSLLLDLDA ADPDEGPNGD VVFAFGARTP PEARRLFRLD
310 320 330 340 350
PRSGRLTLAG PVDYERQDTY ELDVRAQDRG PGPRAATCKV IVRIRDVNDN
360 370 380 390 400
APDIAITPLA APGAPATSPF AAAAAAAALG GADASSPAGA GTPEAGATSL
410 420 430 440 450
VPEGAARESL VALVSTSDRD SGANGQVRCA LYGHEHFRLQ PAYAGSYLVV
460 470 480 490 500
TAASLDRERI AEYNLTLVAE DRGAPPLRTV RPYTVRVGDE NDNAPLFTRP
510 520 530 540 550
VYEVSVRENN PPGAYLATVA ARDRDLGRNG QVTYRLLEAE VGRAGGAVST
560 570 580 590 600
YVSVDPATGA IYALRSFDYE TLRQLDVRIQ ASDGGSPQLS SSALVQVRVL
610 620 630 640 650
DQNDHAPVLV HPAPANGSLE VAVPGRTAKD TVVARVQARD ADEGANGELA
660 670 680 690 700
FELQQQEPRE AFAIGRRTGE ILLTGDLSQE PPGRVFRALL VISDGGRPPL
710 720 730 740 750
TTTATVSFVV TAGGGRGPAA PASAGSPERS RPPGSRLGVS GSVLQWDTPL
760 770 780 790 800
IVIIVLAGSC TLLLAAIIAI ATTCNRRKKE VRKGGALREE RPGAAGGGAS
810 820 830 840 850
APGSPEEAAR GAGPRPNMFD VLTFPGTGKA PFGSPAADAP PPAVAAAEVP
860 870 880 890 900
GSEGGSATGE SACHFEGQQR LRGAHAEPYG ASPGFGKEPA PPVAVWKGHS
910 920 930 940 950
FNTISGREAE KFSGKDSGKG DSDFNDSDSD ISGDALKKDL INHMQSGLWA
960 970 980 990 1000
CTAECKILGH SDRCWSPSCS GPNAHPSPHP PAQMSTFCKS TSLPRDPLRR
1010 1020 1030 1040 1050
DNYYQAQLPK TVGLQSVYEK VLHRDYDRTV TLLSPPRPGR LPDLQEIGVP
1060 1070
LYQSPPGRYL SPKKGANENV
Length:1,070
Mass (Da):113,019
Last modified:May 1, 2000 - v2
Checksum:iCBCCE3C43C0E02D8
GO
Isoform 2 (identifier: O95206-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     780-876: Missing.

Show »
Length:973
Mass (Da):103,633
Checksum:i83F24DB14FE08126
GO

Sequence cautioni

The sequence BAG60019 differs from that shown. Probable cloning artifact.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti39E → K in AAK21986 (PubMed:11230163).Curated1
Sequence conflicti834S → C in AAH36025 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0171717W → R.1 PublicationCorresponds to variant rs3742301dbSNPEnsembl.1
Natural variantiVAR_01717239E → A.1 PublicationCorresponds to variant rs5030683dbSNPEnsembl.1
Natural variantiVAR_059191367T → A.Corresponds to variant rs9596693dbSNPEnsembl.1
Natural variantiVAR_017173743V → A.1 PublicationCorresponds to variant rs5030685dbSNPEnsembl.1
Natural variantiVAR_036108956K → N in a breast cancer sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_008706780 – 876Missing in isoform 2. 1 PublicationAdd BLAST97

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF061573 mRNA. Translation: AAC70009.2.
AY013873 mRNA. Translation: AAK21986.1.
AL139085 Genomic DNA. Translation: CAI14110.1.
AL139085 Genomic DNA. Translation: CAI14111.1.
CH471124 Genomic DNA. Translation: EAW52049.1.
CH471124 Genomic DNA. Translation: EAW52050.1.
BC036025 mRNA. Translation: AAH36025.1.
AK297652 mRNA. Translation: BAG60019.1. Sequence problems.
CCDSiCCDS9438.1. [O95206-1]
CCDS9439.1. [O95206-2]
RefSeqiNP_002581.2. NM_002590.3. [O95206-1]
NP_116567.1. NM_032949.2. [O95206-2]
UniGeneiHs.19492.

Genome annotation databases

EnsembliENST00000338862; ENSP00000341350; ENSG00000136099. [O95206-2]
ENST00000377942; ENSP00000367177; ENSG00000136099. [O95206-1]
GeneIDi5100.
KEGGihsa:5100.
UCSCiuc001vhi.4. human. [O95206-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF061573 mRNA. Translation: AAC70009.2.
AY013873 mRNA. Translation: AAK21986.1.
AL139085 Genomic DNA. Translation: CAI14110.1.
AL139085 Genomic DNA. Translation: CAI14111.1.
CH471124 Genomic DNA. Translation: EAW52049.1.
CH471124 Genomic DNA. Translation: EAW52050.1.
BC036025 mRNA. Translation: AAH36025.1.
AK297652 mRNA. Translation: BAG60019.1. Sequence problems.
CCDSiCCDS9438.1. [O95206-1]
CCDS9439.1. [O95206-2]
RefSeqiNP_002581.2. NM_002590.3. [O95206-1]
NP_116567.1. NM_032949.2. [O95206-2]
UniGeneiHs.19492.

3D structure databases

ProteinModelPortaliO95206.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111133. 2 interactors.
IntActiO95206. 3 interactors.
MINTiMINT-2861561.
STRINGi9606.ENSP00000367177.

PTM databases

iPTMnetiO95206.
PhosphoSitePlusiO95206.

Polymorphism and mutation databases

BioMutaiPCDH8.

Proteomic databases

PaxDbiO95206.
PeptideAtlasiO95206.
PRIDEiO95206.

Protocols and materials databases

DNASUi5100.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338862; ENSP00000341350; ENSG00000136099. [O95206-2]
ENST00000377942; ENSP00000367177; ENSG00000136099. [O95206-1]
GeneIDi5100.
KEGGihsa:5100.
UCSCiuc001vhi.4. human. [O95206-1]

Organism-specific databases

CTDi5100.
DisGeNETi5100.
GeneCardsiPCDH8.
HGNCiHGNC:8660. PCDH8.
HPAiHPA010509.
MIMi603580. gene.
neXtProtiNX_O95206.
OpenTargetsiENSG00000136099.
PharmGKBiPA33007.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3594. Eukaryota.
ENOG410XQHI. LUCA.
GeneTreeiENSGT00850000132246.
HOGENOMiHOG000220892.
HOVERGENiHBG054878.
InParanoidiO95206.
KOiK16499.
OMAiCLIAFDV.
OrthoDBiEOG091G00QD.
PhylomeDBiO95206.
TreeFamiTF352008.

Miscellaneous databases

GeneWikiiPCDH8.
GenomeRNAii5100.
PROiO95206.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136099.
CleanExiHS_PCDH8.
ExpressionAtlasiO95206. baseline and differential.
GenevisibleiO95206. HS.

Family and domain databases

Gene3Di2.60.40.60. 6 hits.
InterProiIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR020894. Cadherin_CS.
IPR013164. Cadherin_N.
IPR030711. Protocadherin-8.
[Graphical view]
PANTHERiPTHR24028:SF46. PTHR24028:SF46. 2 hits.
PfamiPF00028. Cadherin. 5 hits.
PF08266. Cadherin_2. 1 hit.
[Graphical view]
PRINTSiPR00205. CADHERIN.
SMARTiSM00112. CA. 6 hits.
[Graphical view]
SUPFAMiSSF49313. SSF49313. 6 hits.
PROSITEiPS00232. CADHERIN_1. 5 hits.
PS50268. CADHERIN_2. 6 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPCDH8_HUMAN
AccessioniPrimary (citable) accession number: O95206
Secondary accession number(s): B4DMV7
, Q5TAN1, Q5TAN2, Q8IYE9, Q96SF1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 24, 2003
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.