ID CDHR1_HUMAN Reviewed; 859 AA. AC Q96JP9; Q69YZ8; Q8IXY5; DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 05-FEB-2008, sequence version 2. DT 27-MAR-2024, entry version 162. DE RecName: Full=Cadherin-related family member 1 {ECO:0000305}; DE AltName: Full=Photoreceptor cadherin; DE Short=prCAD; DE AltName: Full=Protocadherin-21; DE Flags: Precursor; GN Name=CDHR1 {ECO:0000312|HGNC:HGNC:14550}; GN Synonyms=KIAA1775, PCDH21, PRCAD; 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 [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Retinoblastoma; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-859 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=11597768; DOI=10.1016/s0169-328x(01)00218-2; RA Nakajima D., Nakayama M., Kikuno R., Hirosawa M., Nagase T., Ohara O.; RT "Identification of three novel non-classical cadherin genes through RT comprehensive analysis of large cDNAs."; RL Brain Res. Mol. Brain Res. 94:85-95(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 595-859 (ISOFORM 1). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP INTERACTION WITH PROM1. RX PubMed=18654668; DOI=10.1172/jci35891; RA Yang Z., Chen Y., Lillo C., Chien J., Yu Z., Michaelides M., Klein M., RA Howes K.A., Li Y., Kaminoh Y., Chen H., Zhao C., Chen Y., Al-Sheikh Y.T., RA Karan G., Corbeil D., Escher P., Kamaya S., Li C., Johnson S., RA Frederick J.M., Zhao Y., Wang C., Cameron D.J., Huttner W.B., RA Schorderet D.F., Munier F.L., Moore A.T., Birch D.G., Baehr W., Hunt D.M., RA Williams D.S., Zhang K.; RT "Mutant prominin 1 found in patients with macular degeneration disrupts RT photoreceptor disk morphogenesis in mice."; RL J. Clin. Invest. 118:2908-2916(2008). RN [6] RP INVOLVEMENT IN CORD15. RX PubMed=20805371; DOI=10.1136/jmg.2009.069120; RA Ostergaard E., Batbayli M., Duno M., Vilhelmsen K., Rosenberg T.; RT "Mutations in PCDH21 cause autosomal recessive cone-rod dystrophy."; RL J. Med. Genet. 47:665-669(2010). RN [7] RP VARIANTS THR-212 AND ALA-532. RX PubMed=16288196; RA Bolz H., Ebermann I., Gal A.; RT "Protocadherin-21 (PCDH21), a candidate gene for human retinal RT dystrophies."; RL Mol. Vis. 11:929-933(2005). RN [8] RP VARIANT CORD15 ALA-574. RX PubMed=26350383; DOI=10.1038/srep13902; RA Nikopoulos K., Avila-Fernandez A., Corton M., Lopez-Molina M.I., RA Perez-Carro R., Bontadelli L., Di Gioia S.A., Zurita O., RA Garcia-Sandoval B., Rivolta C., Ayuso C.; RT "Identification of two novel mutations in CDHR1 in consanguineous Spanish RT families with autosomal recessive retinal dystrophy."; RL Sci. Rep. 5:13902-13902(2015). RN [9] RP VARIANT SER-716. RX PubMed=28965847; DOI=10.1016/j.ajhg.2017.08.017; RA De Mori R., Romani M., D'Arrigo S., Zaki M.S., Lorefice E., Tardivo S., RA Biagini T., Stanley V., Musaev D., Fluss J., Micalizzi A., Nuovo S., RA Illi B., Chiapparini L., Di Marcotullio L., Issa M.Y., Anello D., RA Casella A., Ginevrino M., Leggins A.S., Roosing S., Alfonsi R., Rosati J., RA Schot R., Mancini G.M.S., Bertini E., Dobyns W.B., Mazza T., Gleeson J.G., RA Valente E.M.; RT "Hypomorphic Recessive Variants in SUFU Impair the Sonic Hedgehog Pathway RT and Cause Joubert Syndrome with Cranio-facial and Skeletal Defects."; RL Am. J. Hum. Genet. 101:552-563(2017). RN [10] RP VARIANT SER-171. RX PubMed=30120214; DOI=10.1136/jmedgenet-2018-105364; RA de Bruijn S.E., Verbakel S.K., de Vrieze E., Kremer H., Cremers F.P.M., RA Hoyng C.B., van den Born L.I., Roosing S.; RT "Homozygous variants in KIAA1549, encoding a ciliary protein, are RT associated with autosomal recessive retinitis pigmentosa."; RL J. Med. Genet. 55:705-712(2018). CC -!- FUNCTION: Potential calcium-dependent cell-adhesion protein. May be CC required for the structural integrity of the outer segment (OS) of CC photoreceptor cells (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with PROM1. {ECO:0000269|PubMed:18654668}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass membrane CC protein {ECO:0000250}. Note=Localized at the junction between the inner CC and outer segments of rod and cone photoreceptors cells. Confined to CC the base of the OS. Localized on the edges of nascent evaginating disks CC on the side of the OS opposite the connecting cilium. Expressed at CC postnatal day 2 at the apical tip of the rod photoreceptor cells, the CC site of the developing OS. Colocalized with rhodopsin between postnatal CC days 2 and 9 at the base of the growing OS region (By similarity). CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96JP9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96JP9-2; Sequence=VSP_031190, VSP_031191; CC -!- PTM: Undergoes proteolytic cleavage; produces a soluble 95 kDa N- CC terminal fragment and a 25 kDa cell-associated C-terminal fragment. CC {ECO:0000250}. CC -!- DISEASE: Cone-rod dystrophy 15 (CORD15) [MIM:613660]: An autosomal CC recessive retinal dystrophy characterized by retinal pigment deposits CC visible on fundus examination, predominantly in the macular region, and CC initial loss of cone photoreceptors followed by rod degeneration. This CC leads to decreased visual acuity and sensitivity in the central visual CC field, followed by loss of peripheral vision. Severe loss of vision CC occurs earlier than in retinitis pigmentosa, due to cone photoreceptors CC degenerating at a higher rate than rod photoreceptors. CC {ECO:0000269|PubMed:20805371, ECO:0000269|PubMed:26350383}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. 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; AC022389; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC038799; AAH38799.1; -; mRNA. DR EMBL; AB053448; BAB61905.1; -; mRNA. DR EMBL; AL080188; CAH10732.1; -; mRNA. DR CCDS; CCDS53548.1; -. [Q96JP9-2] DR CCDS; CCDS7372.1; -. [Q96JP9-1] DR RefSeq; NP_001165442.1; NM_001171971.2. [Q96JP9-2] DR RefSeq; NP_149091.1; NM_033100.3. [Q96JP9-1] DR AlphaFoldDB; Q96JP9; -. DR SMR; Q96JP9; -. DR BioGRID; 124919; 5. DR IntAct; Q96JP9; 2. DR STRING; 9606.ENSP00000485478; -. DR GlyCosmos; Q96JP9; 3 sites, No reported glycans. DR GlyGen; Q96JP9; 4 sites. DR iPTMnet; Q96JP9; -. DR PhosphoSitePlus; Q96JP9; -. DR BioMuta; CDHR1; -. DR DMDM; 166980558; -. DR jPOST; Q96JP9; -. DR MassIVE; Q96JP9; -. DR PaxDb; 9606-ENSP00000485478; -. DR PeptideAtlas; Q96JP9; -. DR ProteomicsDB; 77001; -. [Q96JP9-1] DR ProteomicsDB; 77002; -. [Q96JP9-2] DR Antibodypedia; 30037; 83 antibodies from 22 providers. DR DNASU; 92211; -. DR Ensembl; ENST00000332904.7; ENSP00000331063.3; ENSG00000148600.15. [Q96JP9-2] DR Ensembl; ENST00000623527.4; ENSP00000485478.1; ENSG00000148600.15. [Q96JP9-1] DR GeneID; 92211; -. DR KEGG; hsa:92211; -. DR MANE-Select; ENST00000623527.4; ENSP00000485478.1; NM_033100.4; NP_149091.1. DR UCSC; uc001kcv.4; human. [Q96JP9-1] DR AGR; HGNC:14550; -. DR CTD; 92211; -. DR DisGeNET; 92211; -. DR GeneCards; CDHR1; -. DR HGNC; HGNC:14550; CDHR1. DR HPA; ENSG00000148600; Group enriched (retina, skin). DR MalaCards; CDHR1; -. DR MIM; 609502; gene. DR MIM; 613660; phenotype. DR neXtProt; NX_Q96JP9; -. DR OpenTargets; ENSG00000148600; -. DR Orphanet; 1872; Cone rod dystrophy. DR Orphanet; 791; Retinitis pigmentosa. DR PharmGKB; PA33005; -. DR VEuPathDB; HostDB:ENSG00000148600; -. DR eggNOG; KOG3594; Eukaryota. DR GeneTree; ENSGT00940000155509; -. DR HOGENOM; CLU_017357_0_0_1; -. DR InParanoid; Q96JP9; -. DR OMA; HYEIALF; -. DR OrthoDB; 5350302at2759; -. DR PhylomeDB; Q96JP9; -. DR TreeFam; TF332908; -. DR PathwayCommons; Q96JP9; -. DR SignaLink; Q96JP9; -. DR BioGRID-ORCS; 92211; 8 hits in 1144 CRISPR screens. DR ChiTaRS; CDHR1; human. DR GenomeRNAi; 92211; -. DR Pharos; Q96JP9; Tbio. DR PRO; PR:Q96JP9; -. DR Proteomes; UP000005640; Chromosome 10. DR RNAct; Q96JP9; Protein. DR Bgee; ENSG00000148600; Expressed in upper arm skin and 116 other cell types or tissues. DR ExpressionAtlas; Q96JP9; baseline and differential. DR GO; GO:0042622; C:photoreceptor outer segment membrane; IEA:Ensembl. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. 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:0045494; P:photoreceptor cell maintenance; IMP:UniProtKB. DR GO; GO:0008594; P:photoreceptor cell morphogenesis; IMP:UniProtKB. DR GO; GO:0035845; P:photoreceptor cell outer segment organization; IMP:UniProtKB. DR CDD; cd11304; Cadherin_repeat; 6. DR Gene3D; 2.60.40.60; Cadherins; 6. DR InterPro; IPR039808; Cadherin. DR InterPro; IPR002126; Cadherin-like_dom. DR InterPro; IPR015919; Cadherin-like_sf. DR InterPro; IPR020894; Cadherin_CS. DR PANTHER; PTHR24027; CADHERIN-23; 1. DR PANTHER; PTHR24027:SF413; CADHERIN-RELATED FAMILY MEMBER 1; 1. DR Pfam; PF00028; Cadherin; 5. DR PRINTS; PR00205; CADHERIN. DR SMART; SM00112; CA; 6. DR SUPFAM; SSF49313; Cadherin-like; 6. DR PROSITE; PS00232; CADHERIN_1; 2. DR PROSITE; PS50268; CADHERIN_2; 6. DR Genevisible; Q96JP9; HS. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Cell adhesion; Cell membrane; KW Cone-rod dystrophy; Glycoprotein; Membrane; Receptor; Reference proteome; KW Repeat; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT CHAIN 20..859 FT /note="Cadherin-related family member 1" FT /id="PRO_0000318498" FT TOPO_DOM 20..700 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 701..721 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 722..859 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 36..135 FT /note="Cadherin 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 136..246 FT /note="Cadherin 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 247..353 FT /note="Cadherin 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 359..472 FT /note="Cadherin 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 473..576 FT /note="Cadherin 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT DOMAIN 573..688 FT /note="Cadherin 6" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043" FT REGION 770..838 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 803..818 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 58 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 89 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 296 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 681..744 FT /note="TLSRSPMAAFLIQTKDNPMKAVGVLAGTMATVVAITVLISTATFWRNKKSNK FT VLPMRRVLRKRP -> VRRLRYMKNSNFPGTTKSVRKPKFKPKKPHSSQGLFLHPHCEI FT ALFNLSNVNLYSRVFQGAAQAS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_031190" FT VAR_SEQ 745..859 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_031191" FT VARIANT 53 FT /note="H -> Q (in dbSNP:rs12781048)" FT /id="VAR_038744" FT VARIANT 171 FT /note="T -> S (in dbSNP:rs759855253)" FT /evidence="ECO:0000269|PubMed:30120214" FT /id="VAR_083318" FT VARIANT 212 FT /note="A -> T (in dbSNP:rs200880106)" FT /evidence="ECO:0000269|PubMed:16288196" FT /id="VAR_038745" FT VARIANT 243 FT /note="A -> V (in dbSNP:rs7086200)" FT /id="VAR_038746" FT VARIANT 532 FT /note="P -> A (in dbSNP:rs143662988)" FT /evidence="ECO:0000269|PubMed:16288196" FT /id="VAR_038747" FT VARIANT 574 FT /note="P -> A (in CORD15)" FT /evidence="ECO:0000269|PubMed:26350383" FT /id="VAR_075501" FT VARIANT 716 FT /note="T -> S (found in a patient with Joubert syndrome; FT uncertain significance)" FT /evidence="ECO:0000269|PubMed:28965847" FT /id="VAR_080429" SQ SEQUENCE 859 AA; 93595 MW; 7D5D9E3E3353039A CRC64; MRRCRWAALA LGLLRLCLAQ ANFAPHFFDN GVGSTNGNMA LFSLPEDTPV GSHVYTLNGT DPEGDPISYH ISFDPSTRSV FSVDPTFGNI TLVEELDRER EDEIEAIISI SDGLNLVAEK VVILVTDAND EAPRFIQEPY VALVPEDIPA GSIIFKVHAV DRDTGSGGSV TYFLQNLHSP FAVDRHSGVL RLQAGATLDY ERSRTHYITV VAKDGGGRLH GADVVFSATT TVTVNVEDVQ DMAPVFVGTP YYGYVYEDTL PGSEVLKVVA MDGDRGKPNR ILYSLVNGND GAFEINETSG AISITQSPAQ LQREVYELHV QVTEMSPAGS PAAQATVPVT IRIVDLNNHP PTFYGESGPQ NRFELSMNEH PPQGEILRGL KITVNDSDQG ANAKFNLQLV GPRGIFRVVP QTVLNEAQVT IIVENSAAID FEKSKVLTFK LLAVEVNTPE KFSSTADVVI QLLDTNDNVP KFDSLYYVAR IPENAPGGSS VVAVTAVDPD TGPWGEVKYS TYGTGADLFL IHPSTGLIYT QPWASLDAEA TARYNFYVKA EDMEGKYSVA EVFITLLDVN DHPPQFGKSV QKKTMVLGTP VKIEAIDEDA EEPNNLVDYS ITHAEPANVF DINSHTGEIW LKNSIRSLDA LHNITPGRDC LWSLEVQAKD RGSPSFSTTA LLKIDITDAE TLSRSPMAAF LIQTKDNPMK AVGVLAGTMA TVVAITVLIS TATFWRNKKS NKVLPMRRVL RKRPSPAPRT IRIEWLKSKS TKAATKFMLK EKPPNENCNN NSPESSLLPR APALPPPPSV APSTGAAQWT VPTVSGSLTP QPTQPPPKPK TMGSPVQSTL ISELKQKFEK KSVHNKAYF //