CAD12_HUMAN
ID CAD12_HUMAN Reviewed; 794 AA.
AC P55289; B2RBT1; B7Z2U6; Q86UD2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 2.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Cadherin-12;
DE AltName: Full=Brain cadherin;
DE Short=BR-cadherin;
DE AltName: Full=Neural type cadherin 2;
DE Short=N-cadherin 2;
DE Flags: Precursor;
GN Name=CDH12;
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] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=7982033; DOI=10.3109/15419069409014199;
RA Tanihara H., Sano K., Heimark R.L., St John T., Suzuki S.;
RT "Cloning of five human cadherins clarifies characteristic features of
RT cadherin extracellular domain and provides further evidence for two
RT structurally different types of cadherin.";
RL Cell Adhes. Commun. 2:15-26(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT MET-68.
RC TISSUE=Brain cortex;
RX PubMed=7731968; DOI=10.1073/pnas.92.9.3702;
RA Selig S., Bruno S., Scharf J.M., Wang C.H., Vitale E., Gilliam T.C.,
RA Kunkel L.M.;
RT "Expressed cadherin pseudogenes are localized to the critical region of the
RT spinal muscular atrophy gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3702-3706(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain, and Testis;
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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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 [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P55289-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P55289-2; Sequence=VSP_056449;
CC -!- TISSUE SPECIFICITY: Brain.
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}.
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DR EMBL; L34057; AAA35623.1; -; mRNA.
DR EMBL; L33477; AAB48539.1; -; mRNA.
DR EMBL; AK295123; BAH11982.1; -; mRNA.
DR EMBL; AK314800; BAG37328.1; -; mRNA.
DR EMBL; AC022139; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC026716; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC034239; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC091938; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093263; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC108089; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC109455; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC138854; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC138940; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC139497; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC140132; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC140171; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471118; EAX10736.1; -; Genomic_DNA.
DR EMBL; BC047608; AAH47608.1; -; mRNA.
DR CCDS; CCDS3890.1; -. [P55289-1]
DR CCDS; CCDS82991.1; -. [P55289-2]
DR PIR; I59372; I59372.
DR RefSeq; NP_001304156.1; NM_001317227.1. [P55289-1]
DR RefSeq; NP_001304157.1; NM_001317228.1. [P55289-2]
DR RefSeq; NP_004052.2; NM_004061.4. [P55289-1]
DR RefSeq; XP_011512229.1; XM_011513927.2.
DR RefSeq; XP_016864409.1; XM_017008920.1.
DR RefSeq; XP_016864410.1; XM_017008921.1.
DR AlphaFoldDB; P55289; -.
DR SMR; P55289; -.
DR BioGRID; 107445; 15.
DR IntAct; P55289; 3.
DR STRING; 9606.ENSP00000371689; -.
DR GlyGen; P55289; 4 sites.
DR iPTMnet; P55289; -.
DR PhosphoSitePlus; P55289; -.
DR BioMuta; CDH12; -.
DR DMDM; 158937438; -.
DR MassIVE; P55289; -.
DR PaxDb; P55289; -.
DR PeptideAtlas; P55289; -.
DR PRIDE; P55289; -.
DR ProteomicsDB; 56839; -. [P55289-1]
DR ProteomicsDB; 6465; -.
DR TopDownProteomics; P55289-2; -. [P55289-2]
DR Antibodypedia; 22634; 287 antibodies from 28 providers.
DR DNASU; 1010; -.
DR Ensembl; ENST00000382254.6; ENSP00000371689.1; ENSG00000154162.15. [P55289-1]
DR Ensembl; ENST00000504376.6; ENSP00000423577.1; ENSG00000154162.15. [P55289-1]
DR Ensembl; ENST00000522262.1; ENSP00000428786.1; ENSG00000154162.15. [P55289-2]
DR GeneID; 1010; -.
DR KEGG; hsa:1010; -.
DR MANE-Select; ENST00000382254.6; ENSP00000371689.1; NM_004061.5; NP_004052.2.
DR UCSC; uc003jgk.3; human. [P55289-1]
DR CTD; 1010; -.
DR DisGeNET; 1010; -.
DR GeneCards; CDH12; -.
DR HGNC; HGNC:1751; CDH12.
DR HPA; ENSG00000154162; Tissue enhanced (brain, retina).
DR MIM; 600562; gene.
DR neXtProt; NX_P55289; -.
DR OpenTargets; ENSG00000154162; -.
DR PharmGKB; PA26285; -.
DR VEuPathDB; HostDB:ENSG00000154162; -.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT00940000154187; -.
DR HOGENOM; CLU_005284_3_1_1; -.
DR InParanoid; P55289; -.
DR OMA; FTRHRPP; -.
DR OrthoDB; 173598at2759; -.
DR PhylomeDB; P55289; -.
DR TreeFam; TF329887; -.
DR PathwayCommons; P55289; -.
DR Reactome; R-HSA-418990; Adherens junctions interactions.
DR SignaLink; P55289; -.
DR SIGNOR; P55289; -.
DR BioGRID-ORCS; 1010; 8 hits in 1068 CRISPR screens.
DR ChiTaRS; CDH12; human.
DR GeneWiki; CDH12; -.
DR GenomeRNAi; 1010; -.
DR Pharos; P55289; Tbio.
DR PRO; PR:P55289; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P55289; protein.
DR Bgee; ENSG00000154162; Expressed in middle temporal gyrus and 92 other tissues.
DR Genevisible; P55289; HS.
DR GO; GO:0005912; C:adherens junction; IBA:GO_Central.
DR GO; GO:0016342; C:catenin complex; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045296; F:cadherin binding; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0034332; P:adherens junction organization; IBA:GO_Central.
DR GO; GO:0016339; P:calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules; IBA:GO_Central.
DR GO; GO:0000902; P:cell morphogenesis; IBA:GO_Central.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; IBA:GO_Central.
DR GO; GO:0007043; P:cell-cell junction assembly; 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; 5.
DR Pfam; PF01049; Cadherin_C; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 5.
DR SUPFAM; SSF49313; SSF49313; 5.
DR PROSITE; PS00232; CADHERIN_1; 2.
DR PROSITE; PS50268; CADHERIN_2; 5.
PE 2: Evidence at transcript level;
KW Alternative splicing; Calcium; Cell adhesion; Cell membrane;
KW Cleavage on pair of basic residues; Glycoprotein; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..54
FT /evidence="ECO:0000255"
FT /id="PRO_0000003791"
FT CHAIN 55..794
FT /note="Cadherin-12"
FT /id="PRO_0000003792"
FT TOPO_DOM 55..609
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 610..637
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 638..794
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 55..160
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 161..269
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 270..384
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 385..487
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 488..609
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT MOD_RES 787
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P97326"
FT CARBOHYD 256
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 456
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 537
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 545
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 176..215
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056449"
FT VARIANT 68
FT /note="V -> M (in dbSNP:rs4371716)"
FT /evidence="ECO:0000269|PubMed:7731968"
FT /id="VAR_048505"
FT VARIANT 284
FT /note="I -> V (in dbSNP:rs17328673)"
FT /id="VAR_048506"
FT VARIANT 475
FT /note="I -> T (in dbSNP:rs12108814)"
FT /id="VAR_048507"
FT CONFLICT 349
FT /note="E -> D (in Ref. 2; AAB48539)"
FT /evidence="ECO:0000305"
FT CONFLICT 416
FT /note="S -> G (in Ref. 1; AAA35623)"
FT /evidence="ECO:0000305"
FT CONFLICT 644
FT /note="D -> H (in Ref. 1; AAA35623)"
FT /evidence="ECO:0000305"
FT CONFLICT 733
FT /note="Y -> I (in Ref. 1; AAA35623)"
FT /evidence="ECO:0000305"
FT CONFLICT 761
FT /note="A -> T (in Ref. 2; AAB48539)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 794 AA; 88332 MW; 76DF39AB56E7BC2D CRC64;
MLTRNCLSLL LWVLFDGGLL TPLQPQPQQT LATEPRENVI HLPGQRSHFQ RVKRGWVWNQ
FFVLEEYVGS EPQYVGKLHS DLDKGEGTVK YTLSGDGAGT VFTIDETTGD IHAIRSLDRE
EKPFYTLRAQ AVDIETRKPL EPESEFIIKV QDINDNEPKF LDGPYVATVP EMSPVGAYVL
QVKATDADDP TYGNSARVVY SILQGQPYFS IDPKTGVIRT ALPNMDREVK EQYQVLIQAK
DMGGQLGGLA GTTIVNITLT DVNDNPPRFP KSIFHLKVPE SSPIGSAIGR IRAVDPDFGQ
NAEIEYNIVP GDGGNLFDIV TDEDTQEGVI KLKKPLDFET KKAYTFKVEA SNLHLDHRFH
SAGPFKDTAT VKISVLDVDE PPVFSKPLYT MEVYEDTPVG TIIGAVTAQD LDVGSSAVRY
FIDWKSDGDS YFTIDGNEGT IATNELLDRE STAQYNFSII ASKVSNPLLT SKVNILINVL
DVNEFPPEIS VPYETAVCEN AKPGQIIQIV SAADRDLSPA GQQFSFRLSP EAAIKPNFTV
RDFRNNTAGI ETRRNGYSRR QQELYFLPVV IEDSSYPVQS STNTMTIRVC RCDSDGTILS
CNVEAIFLPV GLSTGALIAI LLCIVILLAI VVLYVALRRQ KKKDTLMTSK EDIRDNVIHY
DDEGGGEEDT QAFDIGALRN PKVIEENKIR RDIKPDSLCL PRQRPPMEDN TDIRDFIHQR
LQENDVDPTA PPYDSLATYA YEGSGSVAES LSSIDSLTTE ADQDYDYLTD WGPRFKVLAD
MFGEEESYNP DKVT
