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Protein

Protocadherin alpha-4

Gene

PCDHA4

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

Functioni

Calcium-dependent cell-adhesion protein involved in cells self-recognition and non-self discrimination. Thereby, it is involved in the establishment and maintenance of specific neuronal connections in the brain.By similarity

GO - Molecular functioni

GO - Biological processi

  • cell adhesion Source: ProtInc
  • homophilic cell adhesion via plasma membrane adhesion molecules Source: InterPro
  • nervous system development Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Calcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Protocadherin alpha-4Curated
Short name:
PCDH-alpha-4Curated
Gene namesi
Name:PCDHA4Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:8670. PCDHA4.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein By similarity

  • Note: Detected in dendrites and synapses.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini30 – 697ExtracellularBy similarityAdd BLAST668
Transmembranei698 – 718HelicalSequence analysisAdd BLAST21
Topological domaini719 – 947CytoplasmicBy similarityAdd BLAST229

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi56144.
OpenTargetsiENSG00000204967.
PharmGKBiPA33016.

Polymorphism and mutation databases

BioMutaiPCDHA4.
DMDMi13878424.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
ChainiPRO_000000389030 – 947Protocadherin alpha-4Add BLAST918

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi96 ↔ 102By similarity
Glycosylationi139N-linked (GlcNAc...)Sequence analysis1
Glycosylationi257N-linked (GlcNAc...)Sequence analysis1
Glycosylationi265N-linked (GlcNAc...)Sequence analysis1
Glycosylationi548N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9UN74.
PaxDbiQ9UN74.
PeptideAtlasiQ9UN74.
PRIDEiQ9UN74.
TopDownProteomicsiQ9UN74-2. [Q9UN74-2]

PTM databases

iPTMnetiQ9UN74.
PhosphoSitePlusiQ9UN74.

Expressioni

Gene expression databases

ExpressionAtlasiQ9UN74. baseline and differential.
GenevisibleiQ9UN74. HS.

Interactioni

Subunit structurei

Forms homodimers in trans (molecules expressed by two different cells). Forms promiscuous heterodimers in cis (at the plasma membrane of the same cell) with other protocadherins. Interacts with FYN.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
SGTAO437653EBI-712273,EBI-347996

Protein-protein interaction databases

BioGridi121084. 38 interactors.
IntActiQ9UN74. 15 interactors.
MINTiMINT-1368168.
STRINGi9606.ENSP00000435300.

Structurei

3D structure databases

ProteinModelPortaliQ9UN74.
SMRiQ9UN74.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 133Cadherin 1PROSITE-ProRule annotationAdd BLAST104
Domaini134 – 242Cadherin 2PROSITE-ProRule annotationAdd BLAST109
Domaini243 – 350Cadherin 3PROSITE-ProRule annotationAdd BLAST108
Domaini351 – 455Cadherin 4PROSITE-ProRule annotationAdd BLAST105
Domaini456 – 565Cadherin 5PROSITE-ProRule annotationAdd BLAST110
Domaini588 – 678Cadherin 6PROSITE-ProRule annotationAdd BLAST91
Repeati734 – 737PXXP 14
Repeati774 – 777PXXP 24
Repeati796 – 799PXXP 34
Repeati829 – 832PXXP 44
Repeati870 – 873PXXP 54
Repeati888 – 891PXXP 64

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni734 – 8916 X 4 AA repeats of P-X-X-PAdd BLAST158
Regioni738 – 947Required for interaction with FYNBy similarityAdd BLAST210

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi920 – 927Poly-LysSequence analysis8

Domaini

Cadherin 1 to cadherin 4 domains mediate homophilic trans-interaction, the interaction with an identical protocadherin expressed by a neighboring cell. This is a head-to-tail interaction, the cadherin 1 domain interacting with the cadherin 4 domain and the cadherin 2 domain interacting the cadherin 3 domain of the other protocadherin. The cadherin 6 domain mediates promiscuous interactions with protocadherins on the same cell membrane. Each cadherin domain binds three calcium ions.By similarity

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.
InParanoidiQ9UN74.
KOiK16493.
OMAiDNVPDLE.
OrthoDBiEOG091G00KR.
PhylomeDBiQ9UN74.
TreeFamiTF332299.

Family and domain databases

Gene3Di2.60.40.60. 6 hits.
InterProiIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR031904. Cadherin_CBD.
IPR020894. Cadherin_CS.
IPR013164. Cadherin_N.
[Graphical view]
PfamiPF00028. Cadherin. 5 hits.
PF08266. Cadherin_2. 1 hit.
PF15974. Cadherin_tail. 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: Q9UN74-1) [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
MEFSWGSGQE SRRLLLLLLL LAAWEAGNGQ LHYSVSEEAK HGTFVGRIAQ
60 70 80 90 100
DLGLELAELV PRLFRVASKG RGGLLEVNLQ NGILFVNSRI DREELCRRSA
110 120 130 140 150
ECSIHLEVIV DRPLQVFHVD VEVRDINDNP PVFPATQKNL SIAESRPLDS
160 170 180 190 200
RFPLEGASDA DIGENALLTY RLSPNEYFSL EKPPDDELVK GLGLILRKSL
210 220 230 240 250
DREEAPEIFL VLTATDGGKP ELTGTVQLLI TVLDANDNAP AFDRTIYKVR
260 270 280 290 300
LLENVPNGTL VIKLNASDLD EGLNGDIVYS FSNDISPNVK SKFHIDPITG
310 320 330 340 350
QIIVKGYIDF EESKSYEIIV EGIDKGQLPL SGHCRVIVEV EDNNDNVPDL
360 370 380 390 400
EFKSLSLPIR EDAPLGTVIA LISVSDKDMG VNGLVTCSLT SHVPFKLVST
410 420 430 440 450
FKNYYSLVLD SALDRESVSA YELVVTARDG GSPSLWATAS VSVEVADVND
460 470 480 490 500
NAPAFAQPEY TVFVKENNPP GCHIFTVSAW DADAQENALV SYSLVERRVG
510 520 530 540 550
ERALSSYVSV HAESGKVYAL QPLDHEELEL LQFQVTARDA GVPPLGSNVT
560 570 580 590 600
LQVFVLDEND NAPALLAPRA GGTGGAVSEL VPWSVGVGHV VAKVRAVDAD
610 620 630 640 650
SGYNAWLSYE LQPGTGGARI PFRVGLYTGE ISTTRALDET DAPRHRLLVL
660 670 680 690 700
VKDHGEPALT ATATVLVSLV ESGQAPKASS RALVGAVGPD AALVDVNVYL
710 720 730 740 750
IIAICAVSSL LVLTLLLYTA LRCSALPTEG ACAPGKPTLV CSSAVGSWSY
760 770 780 790 800
SQQRRPRVCS GEGPPKTDLM AFSPSLPDSR DREDQLQTTE ESFAKPRQPN
810 820 830 840 850
PDWRYSASLR AGMHSSVHLE EAGILRAGPG GPDQQWPTVS SATPEPEAGE
860 870 880 890 900
VSPPVGAGVN SNSWTFKYGP GNPKQSGPGE LPDKFIIPGS PAIISIRQEP
910 920 930 940
TNSQIDKSDF ITFGKKEETK KKKKKKKGNK TQEKKEKGNS TTDNSDQ
Length:947
Mass (Da):102,293
Last modified:May 1, 2000 - v1
Checksum:i2B06F20872D731D8
GO
Isoform 2 (identifier: Q9UN74-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     796-798: PRQ → VSV
     799-947: Missing.

Show »
Length:798
Mass (Da):86,158
Checksum:i9EF890C30F48A77F
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05918055E → D.Corresponds to variant rs11167605dbSNPEnsembl.1
Natural variantiVAR_024390184P → S.Corresponds to variant rs3822346dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000677796 – 798PRQ → VSV in isoform 2. 2 Publications3
Alternative sequenceiVSP_000678799 – 947Missing in isoform 2. 2 PublicationsAdd BLAST149

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF152312 mRNA. Translation: AAD43706.1.
AF152482 mRNA. Translation: AAD43743.1.
AC005609 Genomic DNA. Translation: AAC34322.1.
BC112102 mRNA. Translation: AAI12103.1.
BC113609 mRNA. Translation: AAI13610.1.
CCDSiCCDS54916.1. [Q9UN74-1]
RefSeqiNP_061730.1. NM_018907.3. [Q9UN74-1]
NP_113688.1. NM_031500.2. [Q9UN74-2]
UniGeneiHs.199343.

Genome annotation databases

EnsembliENST00000530339; ENSP00000435300; ENSG00000204967. [Q9UN74-1]
ENST00000618834; ENSP00000481220; ENSG00000204967. [Q9UN74-2]
GeneIDi56144.
KEGGihsa:56144.
UCSCiuc003lhi.4. human. [Q9UN74-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF152312 mRNA. Translation: AAD43706.1.
AF152482 mRNA. Translation: AAD43743.1.
AC005609 Genomic DNA. Translation: AAC34322.1.
BC112102 mRNA. Translation: AAI12103.1.
BC113609 mRNA. Translation: AAI13610.1.
CCDSiCCDS54916.1. [Q9UN74-1]
RefSeqiNP_061730.1. NM_018907.3. [Q9UN74-1]
NP_113688.1. NM_031500.2. [Q9UN74-2]
UniGeneiHs.199343.

3D structure databases

ProteinModelPortaliQ9UN74.
SMRiQ9UN74.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121084. 38 interactors.
IntActiQ9UN74. 15 interactors.
MINTiMINT-1368168.
STRINGi9606.ENSP00000435300.

PTM databases

iPTMnetiQ9UN74.
PhosphoSitePlusiQ9UN74.

Polymorphism and mutation databases

BioMutaiPCDHA4.
DMDMi13878424.

Proteomic databases

EPDiQ9UN74.
PaxDbiQ9UN74.
PeptideAtlasiQ9UN74.
PRIDEiQ9UN74.
TopDownProteomicsiQ9UN74-2. [Q9UN74-2]

Protocols and materials databases

DNASUi56144.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000530339; ENSP00000435300; ENSG00000204967. [Q9UN74-1]
ENST00000618834; ENSP00000481220; ENSG00000204967. [Q9UN74-2]
GeneIDi56144.
KEGGihsa:56144.
UCSCiuc003lhi.4. human. [Q9UN74-1]

Organism-specific databases

CTDi56144.
DisGeNETi56144.
GeneCardsiPCDHA4.
HGNCiHGNC:8670. PCDHA4.
MIMi604966. gene.
606310. gene.
neXtProtiNX_Q9UN74.
OpenTargetsiENSG00000204967.
PharmGKBiPA33016.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3594. Eukaryota.
ENOG410XQHI. LUCA.
GeneTreeiENSGT00850000132246.
HOGENOMiHOG000220892.
HOVERGENiHBG054878.
InParanoidiQ9UN74.
KOiK16493.
OMAiDNVPDLE.
OrthoDBiEOG091G00KR.
PhylomeDBiQ9UN74.
TreeFamiTF332299.

Miscellaneous databases

GeneWikiiPCDHA4.
GenomeRNAii56144.
PROiQ9UN74.
SOURCEiSearch...

Gene expression databases

ExpressionAtlasiQ9UN74. baseline and differential.
GenevisibleiQ9UN74. HS.

Family and domain databases

Gene3Di2.60.40.60. 6 hits.
InterProiIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR031904. Cadherin_CBD.
IPR020894. Cadherin_CS.
IPR013164. Cadherin_N.
[Graphical view]
PfamiPF00028. Cadherin. 5 hits.
PF08266. Cadherin_2. 1 hit.
PF15974. Cadherin_tail. 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 nameiPCDA4_HUMAN
AccessioniPrimary (citable) accession number: Q9UN74
Secondary accession number(s): O75285, Q2M253
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 143 of the entry and version 1 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 5
    Human chromosome 5: 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.