CADH4_HUMAN
ID CADH4_HUMAN Reviewed; 916 AA.
AC P55283; B3KWB8; G3V1P8; Q2M208; Q5VZ44; Q9BZ05;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 08-NOV-2005, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Cadherin-4;
DE AltName: Full=Retinal cadherin;
DE Short=R-CAD;
DE Short=R-cadherin;
DE Flags: Precursor;
GN Name=CDH4;
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), AND VARIANT ARG-625.
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain cortex;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 393-916 (ISOFORM 1), AND VARIANT ARG-625.
RC TISSUE=Fetal brain;
RX PubMed=2059658; DOI=10.1091/mbc.2.4.261;
RA Suzuki S., Sano K., Tanihara H.;
RT "Diversity of the cadherin family: evidence for eight new cadherins in
RT nervous tissue.";
RL Cell Regul. 2:261-270(1991).
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. May play an important role in retinal
CC development.
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=P55283-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P55283-2; Sequence=VSP_045548;
CC -!- TISSUE SPECIFICITY: Expressed mainly in brain but also found in other
CC tissues.
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; L34059; AAA35627.1; -; mRNA.
DR EMBL; AK124724; BAG54080.1; -; mRNA.
DR EMBL; AL365401; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL162457; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL109911; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL365229; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL079336; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL160412; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391316; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL450463; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX640515; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75409.1; -; Genomic_DNA.
DR EMBL; BC101651; AAI01652.1; -; mRNA.
DR EMBL; BC112150; AAI12151.1; -; mRNA.
DR CCDS; CCDS13488.1; -. [P55283-1]
DR CCDS; CCDS58784.1; -. [P55283-2]
DR PIR; C38992; C38992.
DR RefSeq; NP_001239268.1; NM_001252339.2. [P55283-2]
DR RefSeq; NP_001785.2; NM_001794.4. [P55283-1]
DR AlphaFoldDB; P55283; -.
DR SMR; P55283; -.
DR BioGRID; 107437; 8.
DR IntAct; P55283; 4.
DR MINT; P55283; -.
DR STRING; 9606.ENSP00000484928; -.
DR GlyGen; P55283; 6 sites.
DR iPTMnet; P55283; -.
DR PhosphoSitePlus; P55283; -.
DR BioMuta; CDH4; -.
DR DMDM; 81175161; -.
DR EPD; P55283; -.
DR jPOST; P55283; -.
DR MassIVE; P55283; -.
DR MaxQB; P55283; -.
DR PaxDb; P55283; -.
DR PeptideAtlas; P55283; -.
DR PRIDE; P55283; -.
DR ProteomicsDB; 32401; -.
DR ProteomicsDB; 56833; -. [P55283-1]
DR Antibodypedia; 2666; 334 antibodies from 32 providers.
DR DNASU; 1002; -.
DR Ensembl; ENST00000543233.2; ENSP00000443301.1; ENSG00000179242.16. [P55283-2]
DR Ensembl; ENST00000614565.5; ENSP00000484928.1; ENSG00000179242.16. [P55283-1]
DR GeneID; 1002; -.
DR KEGG; hsa:1002; -.
DR MANE-Select; ENST00000614565.5; ENSP00000484928.1; NM_001794.5; NP_001785.2.
DR UCSC; uc032pok.1; human. [P55283-1]
DR CTD; 1002; -.
DR DisGeNET; 1002; -.
DR GeneCards; CDH4; -.
DR HGNC; HGNC:1763; CDH4.
DR HPA; ENSG00000179242; Tissue enhanced (brain, lymphoid tissue, ovary, skeletal muscle).
DR MIM; 603006; gene.
DR neXtProt; NX_P55283; -.
DR OpenTargets; ENSG00000179242; -.
DR PharmGKB; PA26300; -.
DR VEuPathDB; HostDB:ENSG00000179242; -.
DR eggNOG; KOG3594; Eukaryota.
DR GeneTree; ENSGT00940000158073; -.
DR InParanoid; P55283; -.
DR OMA; QICERPG; -.
DR OrthoDB; 191117at2759; -.
DR PhylomeDB; P55283; -.
DR TreeFam; TF316817; -.
DR PathwayCommons; P55283; -.
DR Reactome; R-HSA-418990; Adherens junctions interactions.
DR Reactome; R-HSA-525793; Myogenesis.
DR SignaLink; P55283; -.
DR SIGNOR; P55283; -.
DR BioGRID-ORCS; 1002; 11 hits in 1071 CRISPR screens.
DR ChiTaRS; CDH4; human.
DR GeneWiki; CDH4; -.
DR GenomeRNAi; 1002; -.
DR Pharos; P55283; Tbio.
DR PRO; PR:P55283; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P55283; protein.
DR Bgee; ENSG00000179242; Expressed in ventricular zone and 89 other tissues.
DR ExpressionAtlas; P55283; baseline and differential.
DR Genevisible; P55283; HS.
DR GO; GO:0016342; C:catenin complex; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; 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:0048675; P:axon extension; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; IEA:Ensembl.
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:0007157; P:heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules; IEA:Ensembl.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IBA:GO_Central.
DR GO; GO:0045773; P:positive regulation of axon extension; IEA:Ensembl.
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; IPR014868; Cadherin_pro_dom.
DR InterPro; IPR027397; Catenin-bd_sf.
DR PANTHER; PTHR24027; PTHR24027; 1.
DR Pfam; PF00028; Cadherin; 4.
DR Pfam; PF01049; Cadherin_C; 1.
DR Pfam; PF08758; Cadherin_pro; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 5.
DR SMART; SM01055; Cadherin_pro; 1.
DR SUPFAM; SSF49313; SSF49313; 6.
DR PROSITE; PS00232; CADHERIN_1; 3.
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 Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..169
FT /evidence="ECO:0000255"
FT /id="PRO_0000003749"
FT CHAIN 170..916
FT /note="Cadherin-4"
FT /id="PRO_0000003750"
FT TOPO_DOM 170..734
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 735..756
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 757..916
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 170..277
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 278..392
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 393..507
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 508..613
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 614..724
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REGION 124..168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 806..838
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 412
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 557
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 632
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 661
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 702
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..74
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045548"
FT VARIANT 141
FT /note="A -> V (in dbSNP:rs34937312)"
FT /id="VAR_048504"
FT VARIANT 625
FT /note="K -> R (in dbSNP:rs6142884)"
FT /evidence="ECO:0000269|PubMed:2059658,
FT ECO:0000269|PubMed:7982033"
FT /id="VAR_033699"
FT CONFLICT 88
FT /note="T -> A (in Ref. 2; BAG54080)"
FT /evidence="ECO:0000305"
FT CONFLICT 223
FT /note="D -> N (in Ref. 1; AAA35627)"
FT /evidence="ECO:0000305"
FT CONFLICT 274
FT /note="R -> H (in Ref. 1; AAA35627)"
FT /evidence="ECO:0000305"
FT CONFLICT 284
FT /note="G -> C (in Ref. 1; AAA35627)"
FT /evidence="ECO:0000305"
FT CONFLICT 299
FT /note="V -> I (in Ref. 1; AAA35627)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="L -> W (in Ref. 1; AAA35627)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="P -> S (in Ref. 1; AAA35627)"
FT /evidence="ECO:0000305"
FT CONFLICT 405
FT /note="R -> S (in Ref. 1; AAA35627 and 6; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 502
FT /note="N -> S (in Ref. 2; BAG54080)"
FT /evidence="ECO:0000305"
FT CONFLICT 540
FT /note="Q -> R (in Ref. 2; BAG54080)"
FT /evidence="ECO:0000305"
FT CONFLICT 566
FT /note="A -> V (in Ref. 1; AAA35627 and 6; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 641
FT /note="D -> H (in Ref. 1; AAA35627 and 6; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 778..779
FT /note="DN -> EK (in Ref. 1; AAA35627 and 6; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 826
FT /note="A -> P (in Ref. 1; AAA35627 and 6; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 916 AA; 100281 MW; E4512F94E58046D7 CRC64;
MTAGAGVLLL LLSLSGALRA HNEDLTTRET CKAGFSEDDY TALISQNILE GEKLLQVKFS
SCVGTKGTQY ETNSMDFKVG ADGTVFATRE LQVPSEQVAF TVTAWDSQTA EKWDAVVRLL
VAQTSSPHSG HKPQKGKKVV ALDPSPPPKD TLLPWPQHQN ANGLRRRKRD WVIPPINVPE
NSRGPFPQQL VRIRSDKDND IPIRYSITGV GADQPPMEVF SIDSMSGRMY VTRPMDREEH
ASYHLRAHAV DMNGNKVENP IDLYIYVIDM NDNRPEFINQ VYNGSVDEGS KPGTYVMTVT
ANDADDSTTA NGMVRYRIVT QTPQSPSQNM FTINSETGDI VTVAAGLDRE KVQQYTVIVQ
ATDMEGNLNY GLSNTATAII TVTDVNDNPP EFTASTFAGE VPENRVETVV ANLTVMDRDQ
PHSPNWNAVY RIISGDPSGH FSVRTDPVTN EGMVTVVKAV DYELNRAFML TVMVSNQAPL
ASGIQMSFQS TAGVTISIMD INEAPYFPSN HKLIRLEEGV PPGTVLTTFS AVDPDRFMQQ
AVRYSKLSDP ASWLHINATN GQITTAAVLD RESLYTKNNV YEATFLAADN GIPPASGTGT
LQIYLIDIND NAPELLPKEA QICEKPNLNA INITAADADV DPNIGPYVFE LPFVPAAVRK
NWTITRLNGD YAQLSLRILY LEAGMYDVPI IVTDSGNPPL SNTSIIKVKV CPCDDNGDCT
TIGAVAAAGL GTGAIVAILI CILILLTMVL LFVMWMKRRE KERHTKQLLI DPEDDVRDNI
LKYDEEGGGE EDQDYDLSQL QQPEAMGHVP SKAPGVRRVD ERPVGAEPQY PIRPMVPHPG
DIGDFINEGL RAADNDPTAP PYDSLLVFDY EGSGSTAGSV SSLNSSSSGD QDYDYLNDWG
PRFKKLADMY GGGEED
