CDHR1_HUMAN
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 03-AUG-2022, entry version 153.
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}; 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 inherited
CC retinal dystrophy characterized by retinal pigment deposits visible on
CC fundus examination, predominantly in the macular region, and initial
CC loss of cone photoreceptors followed by rod degeneration. This leads to
CC decreased visual acuity and sensitivity in the central visual field,
CC followed by loss of peripheral vision. Severe loss of vision occurs
CC 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.
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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 GlyGen; Q96JP9; 4 sites.
DR iPTMnet; Q96JP9; -.
DR PhosphoSitePlus; Q96JP9; -.
DR BioMuta; CDHR1; -.
DR DMDM; 166980558; -.
DR jPOST; Q96JP9; -.
DR MassIVE; Q96JP9; -.
DR PaxDb; Q96JP9; -.
DR PeptideAtlas; Q96JP9; -.
DR PRIDE; Q96JP9; -.
DR ProteomicsDB; 77001; -. [Q96JP9-1]
DR ProteomicsDB; 77002; -. [Q96JP9-2]
DR Antibodypedia; 30037; 67 antibodies from 21 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 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; 237790at2759; -.
DR PhylomeDB; Q96JP9; -.
DR TreeFam; TF332908; -.
DR PathwayCommons; Q96JP9; -.
DR SignaLink; Q96JP9; -.
DR BioGRID-ORCS; 92211; 8 hits in 1066 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 115 other tissues.
DR ExpressionAtlas; Q96JP9; baseline and differential.
DR Genevisible; Q96JP9; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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 InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR020894; Cadherin_CS.
DR Pfam; PF00028; Cadherin; 5.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 6.
DR SUPFAM; SSF49313; SSF49313; 6.
DR PROSITE; PS00232; CADHERIN_1; 2.
DR PROSITE; PS50268; CADHERIN_2; 6.
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 unknown pathological 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