CAD15_HUMAN
ID CAD15_HUMAN Reviewed; 814 AA.
AC P55291;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Cadherin-15;
DE AltName: Full=Cadherin-14;
DE AltName: Full=Muscle cadherin;
DE Short=M-cadherin;
DE Flags: Precursor;
GN Name=CDH15; Synonyms=CDH14, CDH3;
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].
RC TISSUE=Skeletal muscle;
RX PubMed=9030594; DOI=10.1074/jbc.272.8.5236;
RA Shibata T., Shimoyama Y., Gotoh M., Hirohashi S.;
RT "Identification of human cadherin-14, a novel neurally specific type II
RT cadherin, by protein interaction cloning.";
RL J. Biol. Chem. 272:5236-5240(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Muscle;
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 [3]
RP TISSUE SPECIFICITY, CHROMOSOMAL TRANSLOCATION WITH KIRREL3, VARIANTS MRD3
RP LEU-8; CYS-60; TRP-92 AND VAL-122, MUTAGENESIS OF LYS-103 AND MET-109, AND
RP CHARACTERIZATION OF VARIANTS MRD3 CYS-60; TRP-92 AND VAL-122.
RX PubMed=19012874; DOI=10.1016/j.ajhg.2008.10.020;
RA Bhalla K., Luo Y., Buchan T., Beachem M.A., Guzauskas G.F., Ladd S.,
RA Bratcher S.J., Schroer R.J., Balsamo J., DuPont B.R., Lilien J.,
RA Srivastava A.K.;
RT "Alterations in CDH15 and KIRREL3 in patients with mild to severe
RT intellectual disability.";
RL Am. J. Hum. Genet. 83:703-713(2008).
CC -!- FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They
CC preferentially interact with themselves in a homophilic manner in
CC connecting cells; cadherins may thus contribute to the sorting of
CC heterogeneous cell types. M-cadherin is part of the myogenic program
CC and may provide a trigger for terminal muscle differentiation.
CC -!- INTERACTION:
CC P55291; O43765: SGTA; NbExp=8; IntAct=EBI-10215061, EBI-347996;
CC P55291; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-10215061, EBI-744081;
CC P55291; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-10215061, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- TISSUE SPECIFICITY: Expressed in the brain and cerebellum.
CC {ECO:0000269|PubMed:19012874}.
CC -!- DOMAIN: Three calcium ions are usually bound at the interface of each
CC cadherin domain and rigidify the connections, imparting a strong
CC curvature to the full-length ectodomain. {ECO:0000250}.
CC -!- DISEASE: Note=A chromosomal aberration involving CDH15 and KIRREL3 is
CC found in a patient with severe intellectual disability and dysmorphic
CC facial features. Translocation t(11;16)(q24.2;q24).
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 3
CC (MRD3) [MIM:612580]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:19012874}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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DR EMBL; D83542; BAA12012.1; -; mRNA.
DR EMBL; BC008951; AAH08951.1; -; mRNA.
DR CCDS; CCDS10976.1; -.
DR PIR; G02878; G02878.
DR RefSeq; NP_004924.1; NM_004933.2.
DR AlphaFoldDB; P55291; -.
DR SMR; P55291; -.
DR BioGRID; 107448; 14.
DR IntAct; P55291; 3.
DR STRING; 9606.ENSP00000289746; -.
DR GlyGen; P55291; 4 sites.
DR iPTMnet; P55291; -.
DR PhosphoSitePlus; P55291; -.
DR BioMuta; CDH15; -.
DR DMDM; 1705553; -.
DR EPD; P55291; -.
DR jPOST; P55291; -.
DR MassIVE; P55291; -.
DR PaxDb; P55291; -.
DR PeptideAtlas; P55291; -.
DR PRIDE; P55291; -.
DR ProteomicsDB; 56843; -.
DR Antibodypedia; 2417; 312 antibodies from 35 providers.
DR DNASU; 1013; -.
DR Ensembl; ENST00000289746.3; ENSP00000289746.2; ENSG00000129910.8.
DR GeneID; 1013; -.
DR KEGG; hsa:1013; -.
DR MANE-Select; ENST00000289746.3; ENSP00000289746.2; NM_004933.3; NP_004924.1.
DR UCSC; uc002fmt.4; human.
DR CTD; 1013; -.
DR DisGeNET; 1013; -.
DR GeneCards; CDH15; -.
DR HGNC; HGNC:1754; CDH15.
DR HPA; ENSG00000129910; Group enriched (brain, skeletal muscle).
DR MalaCards; CDH15; -.
DR MIM; 114019; gene.
DR MIM; 612580; phenotype.
DR neXtProt; NX_P55291; -.
DR OpenTargets; ENSG00000129910; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR PharmGKB; PA26288; -.
DR VEuPathDB; HostDB:ENSG00000129910; -.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT00940000160118; -.
DR HOGENOM; CLU_005284_2_0_1; -.
DR InParanoid; P55291; -.
DR OMA; TTLYPWR; -.
DR OrthoDB; 395835at2759; -.
DR PhylomeDB; P55291; -.
DR TreeFam; TF316817; -.
DR PathwayCommons; P55291; -.
DR Reactome; R-HSA-418990; Adherens junctions interactions.
DR Reactome; R-HSA-525793; Myogenesis.
DR SignaLink; P55291; -.
DR SIGNOR; P55291; -.
DR BioGRID-ORCS; 1013; 26 hits in 1066 CRISPR screens.
DR GeneWiki; CDH15; -.
DR GenomeRNAi; 1013; -.
DR Pharos; P55291; Tbio.
DR PRO; PR:P55291; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P55291; protein.
DR Bgee; ENSG00000129910; Expressed in cerebellar hemisphere and 110 other tissues.
DR Genevisible; P55291; HS.
DR GO; GO:0016342; C:catenin complex; IBA:GO_Central.
DR GO; GO:0005901; C:caveola; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0045296; F:cadherin binding; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; IBA:GO_Central.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro.
DR Gene3D; 4.10.900.10; -; 1.
DR InterPro; IPR039808; Cadherin.
DR InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR020894; Cadherin_CS.
DR InterPro; IPR000233; Cadherin_cytoplasmic-dom.
DR InterPro; IPR027397; Catenin-bd_sf.
DR PANTHER; PTHR24027; PTHR24027; 1.
DR Pfam; PF00028; Cadherin; 4.
DR Pfam; PF01049; Cadherin_C; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 4.
DR SUPFAM; SSF49313; SSF49313; 5.
DR PROSITE; PS00232; CADHERIN_1; 2.
DR PROSITE; PS50268; CADHERIN_2; 5.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion; Cell membrane; Chromosomal rearrangement;
KW Cleavage on pair of basic residues; Disease variant; Glycoprotein;
KW Intellectual disability; Membrane; Metal-binding; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..60
FT /evidence="ECO:0000255"
FT /id="PRO_0000003805"
FT CHAIN 61..814
FT /note="Cadherin-15"
FT /id="PRO_0000003806"
FT TOPO_DOM 61..606
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 607..626
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 627..814
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 61..152
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 153..260
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 261..375
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 376..481
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 482..590
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REGION 636..663
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 676..703
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 227
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 531
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 538
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 576
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 8
FT /note="V -> L (in MRD3; uncertain pathological
FT significance; dbSNP:rs567903921)"
FT /evidence="ECO:0000269|PubMed:19012874"
FT /id="VAR_054966"
FT VARIANT 60
FT /note="R -> C (in MRD3; affects cell-cell adhesion but not
FT surface expression of the protein; dbSNP:rs121434539)"
FT /evidence="ECO:0000269|PubMed:19012874"
FT /id="VAR_054967"
FT VARIANT 92
FT /note="R -> W (in MRD3; affects cell-cell adhesion but not
FT surface expression of the protein; dbSNP:rs121434540)"
FT /evidence="ECO:0000269|PubMed:19012874"
FT /id="VAR_054968"
FT VARIANT 122
FT /note="A -> V (in MRD3; affects cell-cell adhesion but not
FT surface expression of the protein; dbSNP:rs121434541)"
FT /evidence="ECO:0000269|PubMed:19012874"
FT /id="VAR_054969"
FT MUTAGEN 103
FT /note="K->R: No effect on cell-cell adhesion."
FT /evidence="ECO:0000269|PubMed:19012874"
FT MUTAGEN 109
FT /note="M->T: No effect on cell-cell adhesion."
FT /evidence="ECO:0000269|PubMed:19012874"
SQ SEQUENCE 814 AA; 88916 MW; 618A817DBF2B3343 CRC64;
MDAAFLLVLG LLAQSLCLSL GVPGWRRPTT LYPWRRAPAL SRVRRAWVIP PISVSENHKR
LPYPLVQIKS DKQQLGSVIY SIQGPGVDEE PRGVFSIDKF TGKVFLNAML DREKTDRFRL
RAFALDLGGS TLEDPTDLEI VVVDQNDNRP AFLQEAFTGR VLEGAVPGTY VTRAEATDAD
DPETDNAALR FSILQQGSPE LFSIDELTGE IRTVQVGLDR EVVAVYNLTL QVADMSGDGL
TATASAIITL DDINDNAPEF TRDEFFMEAI EAVSGVDVGR LEVEDRDLPG SPNWVARFTI
LEGDPDGQFT IRTDPKTNEG VLSIVKALDY ESCEHYELKV SVQNEAPLQA AALRAERGQA
KVRVHVQDTN EPPVFQENPL RTSLAEGAPP GTLVATFSAR DPDTEQLQRL SYSKDYDPED
WLQVDAATGR IQTQHVLSPA SPFLKGGWYR AIVLAQDDAS QPRTATGTLS IEILEVNDHA
PVLAPPPPGS LCSEPHQGPG LLLGATDEDL PPHGAPFHFQ LSPRLPELGR NWSLSQVNVS
HARLRPRHQV PEGLHRLSLL LRDSGQPPQQ REQPLNVTVC RCGKDGVCLP GAAALLAGGT
GLSLGALVIV LASALLLLVL VLLVALRARF WKQSRGKGLL HGPQDDLRDN VLNYDEQGGG
EEDQDAYDIS QLRHPTALSL PLGPPPLRRD APQGRLHPQP PRVLPTSPLD IADFINDGLE
AADSDPSVPP YDTALIYDYE GDGSVAGTLS SILSSQGDED QDYDYLRDWG PRFARLADMY
GHPCGLEYGA RWDHQAREGL SPGALLPRHR GRTA
