PCDA4_HUMAN
ID PCDA4_HUMAN Reviewed; 947 AA.
AC Q9UN74; O75285; Q2M253;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Protocadherin alpha-4 {ECO:0000305};
DE Short=PCDH-alpha-4 {ECO:0000305};
DE Flags: Precursor;
GN Name=PCDHA4 {ECO:0000312|HGNC:HGNC:8670};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
RX PubMed=10380929; DOI=10.1016/s0092-8674(00)80789-8;
RA Wu Q., Maniatis T.;
RT "A striking organization of a large family of human neural cadherin-like
RT cell adhesion genes.";
RL Cell 97:779-790(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
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).
CC -!- FUNCTION: Calcium-dependent cell-adhesion protein involved in cells
CC self-recognition and non-self discrimination. Thereby, it is involved
CC in the establishment and maintenance of specific neuronal connections
CC in the brain. {ECO:0000250|UniProtKB:O88689}.
CC -!- SUBUNIT: Forms homodimers in trans (molecules expressed by two
CC different cells). Forms promiscuous heterodimers in cis (at the plasma
CC membrane of the same cell) with other protocadherins. Interacts with
CC FYN. {ECO:0000250|UniProtKB:O88689}.
CC -!- INTERACTION:
CC Q9UN74; O43765: SGTA; NbExp=3; IntAct=EBI-712273, EBI-347996;
CC Q9UN74-2; Q9UMX0: UBQLN1; NbExp=3; IntAct=EBI-12184485, EBI-741480;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O88689};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:O88689}.
CC Note=Detected in dendrites and synapses.
CC {ECO:0000250|UniProtKB:O88689}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UN74-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UN74-2; Sequence=VSP_000677, VSP_000678;
CC -!- DOMAIN: Cadherin 1 to cadherin 4 domains mediate homophilic trans-
CC interaction, the interaction with an identical protocadherin expressed
CC by a neighboring cell. This is a head-to-tail interaction, the cadherin
CC 1 domain interacting with the cadherin 4 domain and the cadherin 2
CC domain interacting the cadherin 3 domain of the other protocadherin.
CC The cadherin 6 domain mediates promiscuous interactions with
CC protocadherins on the same cell membrane. Each cadherin domain binds
CC three calcium ions. {ECO:0000250|UniProtKB:O88689}.
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; AF152312; AAD43706.1; -; mRNA.
DR EMBL; AF152482; AAD43743.1; -; mRNA.
DR EMBL; AC005609; AAC34322.1; -; Genomic_DNA.
DR EMBL; BC112102; AAI12103.1; -; mRNA.
DR EMBL; BC113609; AAI13610.1; -; mRNA.
DR CCDS; CCDS54916.1; -. [Q9UN74-1]
DR RefSeq; NP_061730.1; NM_018907.3. [Q9UN74-1]
DR RefSeq; NP_113688.1; NM_031500.2. [Q9UN74-2]
DR AlphaFoldDB; Q9UN74; -.
DR SMR; Q9UN74; -.
DR BioGRID; 121084; 61.
DR IntAct; Q9UN74; 40.
DR STRING; 9606.ENSP00000435300; -.
DR GlyGen; Q9UN74; 4 sites.
DR iPTMnet; Q9UN74; -.
DR PhosphoSitePlus; Q9UN74; -.
DR BioMuta; PCDHA4; -.
DR DMDM; 13878424; -.
DR jPOST; Q9UN74; -.
DR MassIVE; Q9UN74; -.
DR PaxDb; Q9UN74; -.
DR PeptideAtlas; Q9UN74; -.
DR PRIDE; Q9UN74; -.
DR ProteomicsDB; 85264; -. [Q9UN74-1]
DR ProteomicsDB; 85265; -. [Q9UN74-2]
DR TopDownProteomics; Q9UN74-2; -. [Q9UN74-2]
DR Antibodypedia; 27119; 111 antibodies from 18 providers.
DR DNASU; 56144; -.
DR Ensembl; ENST00000530339.2; ENSP00000435300.1; ENSG00000204967.12. [Q9UN74-1]
DR Ensembl; ENST00000618834.1; ENSP00000481220.1; ENSG00000204967.12. [Q9UN74-2]
DR GeneID; 56144; -.
DR KEGG; hsa:56144; -.
DR MANE-Select; ENST00000530339.2; ENSP00000435300.1; NM_018907.4; NP_061730.1.
DR UCSC; uc003lhi.4; human. [Q9UN74-1]
DR CTD; 56144; -.
DR DisGeNET; 56144; -.
DR GeneCards; PCDHA4; -.
DR HGNC; HGNC:8670; PCDHA4.
DR HPA; ENSG00000204967; Tissue enhanced (brain).
DR MIM; 604966; gene.
DR MIM; 606310; gene.
DR neXtProt; NX_Q9UN74; -.
DR OpenTargets; ENSG00000204967; -.
DR PharmGKB; PA33016; -.
DR VEuPathDB; HostDB:ENSG00000204967; -.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT00940000163846; -.
DR HOGENOM; CLU_006480_0_1_1; -.
DR InParanoid; Q9UN74; -.
DR OMA; FIARFEI; -.
DR PhylomeDB; Q9UN74; -.
DR TreeFam; TF332299; -.
DR PathwayCommons; Q9UN74; -.
DR SignaLink; Q9UN74; -.
DR SIGNOR; Q9UN74; -.
DR BioGRID-ORCS; 56144; 35 hits in 1029 CRISPR screens.
DR GeneWiki; PCDHA4; -.
DR GenomeRNAi; 56144; -.
DR Pharos; Q9UN74; Tdark.
DR PRO; PR:Q9UN74; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9UN74; protein.
DR Bgee; ENSG00000204967; Expressed in cortical plate and 81 other tissues.
DR ExpressionAtlas; Q9UN74; baseline and differential.
DR Genevisible; Q9UN74; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IBA:GO_Central.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR031904; Cadherin_CBD.
DR InterPro; IPR020894; Cadherin_CS.
DR InterPro; IPR013164; Cadherin_N.
DR Pfam; PF00028; Cadherin; 5.
DR Pfam; PF08266; Cadherin_2; 1.
DR Pfam; PF15974; Cadherin_tail; 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 Disulfide bond; Glycoprotein; Membrane; Metal-binding; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..947
FT /note="Protocadherin alpha-4"
FT /id="PRO_0000003890"
FT TOPO_DOM 30..697
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O88689"
FT TRANSMEM 698..718
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 719..947
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O88689"
FT DOMAIN 30..133
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 134..242
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 243..350
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 351..455
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 456..565
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 588..678
FT /note="Cadherin 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REPEAT 734..737
FT /note="PXXP 1"
FT REPEAT 774..777
FT /note="PXXP 2"
FT REPEAT 796..799
FT /note="PXXP 3"
FT REPEAT 829..832
FT /note="PXXP 4"
FT REPEAT 870..873
FT /note="PXXP 5"
FT REPEAT 888..891
FT /note="PXXP 6"
FT REGION 734..891
FT /note="6 X 4 AA repeats of P-X-X-P"
FT REGION 738..947
FT /note="Required for interaction with FYN"
FT /evidence="ECO:0000250|UniProtKB:O88689"
FT REGION 754..805
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 828..853
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 868..947
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 895..909
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 932..947
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 265
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 548
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 96..102
FT /evidence="ECO:0000250|UniProtKB:O88689"
FT VAR_SEQ 796..798
FT /note="PRQ -> VSV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10380929,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_000677"
FT VAR_SEQ 799..947
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10380929,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_000678"
FT VARIANT 55
FT /note="E -> D (in dbSNP:rs11167605)"
FT /id="VAR_059180"
FT VARIANT 184
FT /note="P -> S (in dbSNP:rs3822346)"
FT /id="VAR_024390"
SQ SEQUENCE 947 AA; 102293 MW; 2B06F20872D731D8 CRC64;
MEFSWGSGQE SRRLLLLLLL LAAWEAGNGQ LHYSVSEEAK HGTFVGRIAQ DLGLELAELV
PRLFRVASKG RGGLLEVNLQ NGILFVNSRI DREELCRRSA ECSIHLEVIV DRPLQVFHVD
VEVRDINDNP PVFPATQKNL SIAESRPLDS RFPLEGASDA DIGENALLTY RLSPNEYFSL
EKPPDDELVK GLGLILRKSL DREEAPEIFL VLTATDGGKP ELTGTVQLLI TVLDANDNAP
AFDRTIYKVR LLENVPNGTL VIKLNASDLD EGLNGDIVYS FSNDISPNVK SKFHIDPITG
QIIVKGYIDF EESKSYEIIV EGIDKGQLPL SGHCRVIVEV EDNNDNVPDL EFKSLSLPIR
EDAPLGTVIA LISVSDKDMG VNGLVTCSLT SHVPFKLVST FKNYYSLVLD SALDRESVSA
YELVVTARDG GSPSLWATAS VSVEVADVND NAPAFAQPEY TVFVKENNPP GCHIFTVSAW
DADAQENALV SYSLVERRVG ERALSSYVSV HAESGKVYAL QPLDHEELEL LQFQVTARDA
GVPPLGSNVT LQVFVLDEND NAPALLAPRA GGTGGAVSEL VPWSVGVGHV VAKVRAVDAD
SGYNAWLSYE LQPGTGGARI PFRVGLYTGE ISTTRALDET DAPRHRLLVL VKDHGEPALT
ATATVLVSLV ESGQAPKASS RALVGAVGPD AALVDVNVYL IIAICAVSSL LVLTLLLYTA
LRCSALPTEG ACAPGKPTLV CSSAVGSWSY SQQRRPRVCS GEGPPKTDLM AFSPSLPDSR
DREDQLQTTE ESFAKPRQPN PDWRYSASLR AGMHSSVHLE EAGILRAGPG GPDQQWPTVS
SATPEPEAGE VSPPVGAGVN SNSWTFKYGP GNPKQSGPGE LPDKFIIPGS PAIISIRQEP
TNSQIDKSDF ITFGKKEETK KKKKKKKGNK TQEKKEKGNS TTDNSDQ
