ID   PTHD3_HUMAN             Reviewed;         954 AA.
AC   Q3KNS1; F6LPT1; I3L499; Q6ZU28;
DT   13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT   25-MAY-2022, sequence version 4.
DT   24-JAN-2024, entry version 124.
DE   RecName: Full=Patched domain-containing protein 3;
DE   AltName: Full=Patched-related protein;
GN   Name=PTCHD3; Synonyms=PTR;
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] {ECO:0000312|EMBL:AEA72435.1}
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION,
RP   TISSUE SPECIFICITY, POLYMORPHISM, AND VARIANT GLY-473.
RC   TISSUE=Lymph node {ECO:0000312|EMBL:AEA72435.1};
RX   PubMed=21439084; DOI=10.1186/1471-2350-12-45;
RA   Ghahramani Seno M.M., Kwan B.Y., Lee-Ng K.K., Moessner R., Lionel A.C.,
RA   Marshall C.R., Scherer S.W.;
RT   "Human PTCHD3 nulls: rare copy number and sequence variants suggest a non-
RT   essential gene.";
RL   BMC Med. Genet. 12:45-45(2011).
RN   [2]
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-804, AND VARIANTS GLY-473;
RP   THR-521 AND MET-584.
RC   TISSUE=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 MRNA] OF 1-767, AND VARIANTS PRO-152 AND
RP   MET-584.
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   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=17904097; DOI=10.1016/j.bbrc.2007.09.047;
RA   Fan J., Akabane H., Zheng X., Zhou X., Zhang L., Liu Q., Zhang Y.-L.,
RA   Yang J., Zhu G.-Z.;
RT   "Male germ cell-specific expression of a novel patched-domain containing
RT   gene Ptchd3.";
RL   Biochem. Biophys. Res. Commun. 363:757-761(2007).
CC   -!- FUNCTION: May play a role in sperm development or sperm function
CC       (PubMed:17904097). However, does not appear to have an essential role
CC       in spermatogenesis or male fertility (PubMed:21439084).
CC       {ECO:0000269|PubMed:17904097, ECO:0000269|PubMed:21439084}.
CC   -!- INTERACTION:
CC       Q3KNS1; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-2860313, EBI-10961624;
CC   -!- SUBCELLULAR LOCATION: Cell projection, cilium, flagellum membrane
CC       {ECO:0000269|PubMed:17904097}; Multi-pass membrane protein
CC       {ECO:0000255}. Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:21439084}; Multi-pass membrane protein
CC       {ECO:0000255}. Note=Localizes to the midpiece of the sperm tail.
CC       {ECO:0000269|PubMed:17904097}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q3KNS1-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q3KNS1-2; Sequence=VSP_061519, VSP_061520;
CC   -!- TISSUE SPECIFICITY: Expressed in germ cells of the testis (at protein
CC       level) (PubMed:17904097). Detected in blood lymph, colon, small
CC       intestine, ovary, testis, prostate, thymus and spleen with highest
CC       levels in testis (PubMed:21439084). {ECO:0000269|PubMed:17904097,
CC       ECO:0000269|PubMed:21439084}.
CC   -!- POLYMORPHISM: A stop codon in the gene coding for this protein at
CC       position Glu-768 is responsible for functional diversity thus producing
CC       a pseudogene. {ECO:0000305}.
CC   -!- POLYMORPHISM: The copy number of PTCHD3 varies between individuals with
CC       some individuals having no copy of the gene due to a 102,624 base pair
CC       deletion spanning the PTCHD3 gene. This deletion does not appear to be
CC       associated with an overt phenotype and is found in 0.6-1.6% of
CC       individuals of European ancestry. {ECO:0000269|PubMed:21439084}.
CC   -!- SIMILARITY: Belongs to the patched family. {ECO:0000305}.
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DR   EMBL; JF332167; AEA72435.1; -; mRNA.
DR   EMBL; AL355493; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AK126025; BAC86399.1; -; mRNA.
DR   EMBL; BC107139; AAI07140.1; -; mRNA.
DR   RefSeq; NP_001030014.2; NM_001034842.3.
DR   AlphaFoldDB; Q3KNS1; -.
DR   SMR; Q3KNS1; -.
DR   BioGRID; 131890; 30.
DR   IntAct; Q3KNS1; 4.
DR   GlyCosmos; Q3KNS1; 6 sites, No reported glycans.
DR   GlyGen; Q3KNS1; 7 sites, 1 O-linked glycan (1 site).
DR   iPTMnet; Q3KNS1; -.
DR   PhosphoSitePlus; Q3KNS1; -.
DR   BioMuta; PTCHD3; -.
DR   DMDM; 425906063; -.
DR   jPOST; Q3KNS1; -.
DR   MassIVE; Q3KNS1; -.
DR   PaxDb; 9606-ENSP00000417658; -.
DR   PeptideAtlas; Q3KNS1; -.
DR   DNASU; 374308; -.
DR   GeneID; 374308; -.
DR   KEGG; hsa:374308; -.
DR   UCSC; uc001itu.3; human. [Q3KNS1-1]
DR   AGR; HGNC:24776; -.
DR   CTD; 374308; -.
DR   DisGeNET; 374308; -.
DR   GeneCards; PTCHD3; -.
DR   HGNC; HGNC:24776; PTCHD3.
DR   MIM; 611791; gene.
DR   neXtProt; NX_Q3KNS1; -.
DR   PharmGKB; PA142671117; -.
DR   eggNOG; KOG1934; Eukaryota.
DR   HOGENOM; CLU_002359_2_2_1; -.
DR   InParanoid; Q3KNS1; -.
DR   OrthoDB; 2876883at2759; -.
DR   PhylomeDB; Q3KNS1; -.
DR   TreeFam; TF331806; -.
DR   PathwayCommons; Q3KNS1; -.
DR   SignaLink; Q3KNS1; -.
DR   BioGRID-ORCS; 374308; 12 hits in 1141 CRISPR screens.
DR   ChiTaRS; PTCHD3; human.
DR   GenomeRNAi; 374308; -.
DR   Pharos; Q3KNS1; Tbio.
DR   PRO; PR:Q3KNS1; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q3KNS1; Protein.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-KW.
DR   GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB.
DR   Gene3D; 1.20.1640.10; Multidrug efflux transporter AcrB transmembrane domain; 2.
DR   InterPro; IPR003392; Ptc/Disp.
DR   InterPro; IPR000731; SSD.
DR   PANTHER; PTHR10796:SF60; PATCHED DOMAIN-CONTAINING PROTEIN 3; 1.
DR   PANTHER; PTHR10796; PATCHED-RELATED; 1.
DR   Pfam; PF02460; Patched; 1.
DR   SUPFAM; SSF82866; Multidrug efflux transporter AcrB transmembrane domain; 2.
DR   PROSITE; PS50156; SSD; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Cell projection; Cilium;
KW   Endoplasmic reticulum; Flagellum; Glycoprotein; Membrane;
KW   Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..954
FT                   /note="Patched domain-containing protein 3"
FT                   /id="PRO_0000309262"
FT   TRANSMEM        139..159
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        297..317
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        383..403
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        423..443
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        447..467
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        486..506
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        520..540
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        603..623
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        804..824
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        826..846
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        858..878
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        894..914
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        927..947
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          383..540
FT                   /note="SSD"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT   REGION          1..103
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        24..40
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        43..57
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        192
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        275
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        279
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        678
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        692
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        737
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         511..533
FT                   /note="SVQCFCIYTGMTLLFCYFYNITC -> ASFRQQMFLPQPKRKYCYSNYDA
FT                   (in isoform 2)"
FT                   /id="VSP_061519"
FT   VAR_SEQ         534..954
FT                   /note="Missing (in isoform 2)"
FT                   /id="VSP_061520"
FT   VARIANT         126
FT                   /note="T -> A (in dbSNP:rs12098477)"
FT                   /id="VAR_036918"
FT   VARIANT         152
FT                   /note="L -> P (in dbSNP:rs6482626)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_036919"
FT   VARIANT         224
FT                   /note="A -> G (in dbSNP:rs12098562)"
FT                   /id="VAR_036920"
FT   VARIANT         372
FT                   /note="R -> K (in dbSNP:rs2152099)"
FT                   /id="VAR_036921"
FT   VARIANT         407
FT                   /note="C -> G (in dbSNP:rs2484180)"
FT                   /id="VAR_036922"
FT   VARIANT         473
FT                   /note="D -> G (in dbSNP:rs2429485)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:21439084"
FT                   /id="VAR_036923"
FT   VARIANT         521
FT                   /note="M -> T (in dbSNP:rs2505327)"
FT                   /evidence="ECO:0000269|PubMed:14702039"
FT                   /id="VAR_036924"
FT   VARIANT         584
FT                   /note="I -> M (in dbSNP:rs1638630)"
FT                   /evidence="ECO:0000269|PubMed:14702039,
FT                   ECO:0000269|PubMed:15489334"
FT                   /id="VAR_036925"
FT   CONFLICT        404
FT                   /note="R -> G (in Ref. 3; BAC86399)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   954 AA;  107689 MW;  7028A3C233858CC1 CRC64;
     MPWVEPKPRP GPEQKPKLTK PDSATGPQWY QESQESESEG KQPPPGPLAP PKSPEPSGPL
     ASEQDAPLPE GDDAPPRPSM LDDAPRLPLE LDDAPLPEEE TPEPTAICRH RHRCHTDCLE
     GLLSRTFQWL GWQVGAHPWI FLLAPLMLTA ALGTGFLYLP KDEEEDLEEH YTPVGSPAKA
     ERRFVQGHFT TNDSYRFSAS RRSTEANFVS LLVVSYSDSL LDPATFAEVS KLDGAVQDLR
     VAREKGSQIQ YQQVCARYRA LCVPPNPILY AWQVNKTLNL SSISFPAYNH GRHPLYLTGF
     FGGYILGGSL GMGQLLLRAK AMRLLYYLKT EDPEYDVQSK QWLTHLLDQF TNIKNILALK
     KIEVVHFTSL SRQLEFEATS VTVIPVFHLA YILIILFAVT SCFRFDCIRN KMCVAAFGVI
     SAFLAVVSGF GLLLHIGVPF VIIVANSPFL ILGVGVDDMF IMISAWHKTN LADDIRERMS
     NVYSKAAVSI TITTITNILA LYTGIMSSFR SVQCFCIYTG MTLLFCYFYN ITCFGAFMAL
     DGKREVVCLC WLKKADPKWP SFKKFCCFPF GSVPDEHGTD IHPISLFFRD YFGPFLTRSE
     SKYFVVFIYV LYIISSIYGC FHVQEGLDLR NLASDDSYIT PYFNVEENYF SDYGPRVMVI
     VTKKVDYWDK DVRQKLENCT KIFEKNVYVD KNLTEFWLDA YVQYLKGNSQ DPNEKNTFMN
     NIPDFLSNFP NFQHDINISS SNEIISSRGF IQTTDVSSSA KKKILLFQLR RIAEDCQIPL
     MVYNQAFIYF DQYAAILEDT VRNVLVASAA MFIVSLLLIP YPLCSLWVTF AIGSVIVGVT
     GFMAFWKVNL DSISMINLVI CIGFSFDFSV HISYAFVSSS QPSVNQKSVE ALYLLGYPVL
     QSAISTIIGV CVLAAAKAYI FRTFFKIMFL VMIFGAAHGL IFIPVFLTFF GRFI
//