PTHD4_HUMAN
ID PTHD4_HUMAN Reviewed; 846 AA.
AC Q6ZW05; A0A0A7EN49; B0QZ29; B2RPC0; B4DRK3; B4DTR9; Q5T884;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-NOV-2009, sequence version 3.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=Patched domain-containing protein 4;
DE AltName: Full=p53-regulated patched protein;
GN Name=PTCHD4; Synonyms=C6orf138, PTCH53;
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 3), FUNCTION, AND INDUCTION BY TP53.
RX PubMed=25296753; DOI=10.1074/jbc.m114.597203;
RA Chung J.H., Larsen A.R., Chen E., Bunz F.;
RT "A PTCH1 homolog transcriptionally activated by p53 suppresses hedgehog
RT signaling.";
RL J. Biol. Chem. 289:33020-33031(2014).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
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=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [4]
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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: Could act as a repressor of canonical hedgehog signaling by
CC antagonizing the effects of SMO, as suggested by down-regulation of
CC hedgehog target genes, including GLI1, PTCH1, and PTCH2 in PTCHD4-
CC expressing cells. {ECO:0000269|PubMed:25296753}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q6ZW05-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6ZW05-2; Sequence=VSP_056623, VSP_056624, VSP_056625;
CC Name=3;
CC IsoId=Q6ZW05-3; Sequence=VSP_058428;
CC Name=4;
CC IsoId=Q6ZW05-4; Sequence=VSP_058427;
CC -!- INDUCTION: Induced by TP53. {ECO:0000269|PubMed:25296753}.
CC -!- SIMILARITY: Belongs to the patched family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI37360.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI37365.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC85703.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC85703.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=EAX04325.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AK123835; BAC85703.1; ALT_SEQ; mRNA.
DR EMBL; AK299301; BAG61315.1; -; mRNA.
DR EMBL; AK300335; BAG62081.1; -; mRNA.
DR EMBL; KJ534581; AIY68042.1; -; mRNA.
DR EMBL; AL161622; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139336; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL121973; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353138; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX04325.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC136779; AAI36780.1; -; mRNA.
DR EMBL; BC137359; AAI37360.1; ALT_INIT; mRNA.
DR EMBL; BC137364; AAI37365.1; ALT_INIT; mRNA.
DR CCDS; CCDS34473.2; -. [Q6ZW05-1]
DR RefSeq; NP_001013754.3; NM_001013732.3. [Q6ZW05-1]
DR RefSeq; NP_997382.2; NM_207499.2.
DR RefSeq; XP_011512941.1; XM_011514639.2. [Q6ZW05-4]
DR RefSeq; XP_016866382.1; XM_017010893.1.
DR AlphaFoldDB; Q6ZW05; -.
DR SMR; Q6ZW05; -.
DR STRING; 9606.ENSP00000341914; -.
DR GlyGen; Q6ZW05; 1 site.
DR iPTMnet; Q6ZW05; -.
DR PhosphoSitePlus; Q6ZW05; -.
DR BioMuta; PTCHD4; -.
DR DMDM; 269849699; -.
DR PaxDb; Q6ZW05; -.
DR PeptideAtlas; Q6ZW05; -.
DR PRIDE; Q6ZW05; -.
DR ProteomicsDB; 2721; -.
DR ProteomicsDB; 68451; -. [Q6ZW05-1]
DR Antibodypedia; 48920; 99 antibodies from 19 providers.
DR DNASU; 442213; -.
DR Ensembl; ENST00000339488.9; ENSP00000341914.5; ENSG00000244694.8. [Q6ZW05-3]
DR GeneID; 442213; -.
DR KEGG; hsa:442213; -.
DR MANE-Select; ENST00000339488.9; ENSP00000341914.5; NM_001384253.1; NP_001371182.1. [Q6ZW05-3]
DR UCSC; uc011dwm.2; human. [Q6ZW05-1]
DR CTD; 442213; -.
DR DisGeNET; 442213; -.
DR GeneCards; PTCHD4; -.
DR HGNC; HGNC:21345; PTCHD4.
DR HPA; ENSG00000244694; Low tissue specificity.
DR MIM; 616908; gene.
DR neXtProt; NX_Q6ZW05; -.
DR OpenTargets; ENSG00000244694; -.
DR PharmGKB; PA134982541; -.
DR VEuPathDB; HostDB:ENSG00000244694; -.
DR eggNOG; KOG1934; Eukaryota.
DR GeneTree; ENSGT00940000156827; -.
DR HOGENOM; CLU_002359_2_1_1; -.
DR InParanoid; Q6ZW05; -.
DR OMA; HTSHHET; -.
DR OrthoDB; 210960at2759; -.
DR PhylomeDB; Q6ZW05; -.
DR TreeFam; TF331806; -.
DR PathwayCommons; Q6ZW05; -.
DR BioGRID-ORCS; 442213; 21 hits in 1067 CRISPR screens.
DR ChiTaRS; PTCHD4; human.
DR GenomeRNAi; 442213; -.
DR Pharos; Q6ZW05; Tbio.
DR PRO; PR:Q6ZW05; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q6ZW05; protein.
DR Bgee; ENSG00000244694; Expressed in stromal cell of endometrium and 86 other tissues.
DR ExpressionAtlas; Q6ZW05; baseline and differential.
DR Genevisible; Q6ZW05; HS.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR InterPro; IPR003392; Ptc/Disp.
DR InterPro; IPR000731; SSD.
DR Pfam; PF02460; Patched; 1.
DR PROSITE; PS50156; SSD; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Glycoprotein; Membrane; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..846
FT /note="Patched domain-containing protein 4"
FT /id="PRO_0000320640"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 265..285
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 293..313
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 336..356
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 373..393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 465..485
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 660..680
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 686..706
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 718..738
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 765..785
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 787..807
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 233..392
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT CARBOHYD 762
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..253
FT /note="Missing (in isoform 4)"
FT /id="VSP_058427"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056623"
FT VAR_SEQ 1..4
FT /note="MCFL -> M (in isoform 3)"
FT /id="VSP_058428"
FT VAR_SEQ 304..311
FT /note="HGTKGVFE -> ISTEFTSS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056624"
FT VAR_SEQ 312..846
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056625"
FT CONFLICT 466
FT /note="F -> L (in Ref. 2; BAG62081)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 846 AA; 96371 MW; 2B82D1EB3519F0C6 CRC64;
MCFLRRPGAP ASWIWWRMLR QVLRRGLQSF CHRLGLCVSR HPVFFLTVPA VLTITFGLSA
LNRFQPEGDL ERLVAPSHSL AKIERSLASS LFPLDQSKSQ LYSDLHTPGR YGRVILLSPT
GDNILLQAEG ILQTHRAVLE MKDGRNSFIG HQLGGVVEVP NSKDQRVKSA RAIQITYYLQ
TYGSATQDLI GEKWENEFCK LIRKLQEEHQ ELQLYSLASF SLWRDFHKTS ILARSKVLVS
LVLILTTATL SSSMKDCLRS KPFLGLLGVL TVCISIITAA GIFFITDGKY NSTLLGIPFF
AMGHGTKGVF ELLSGWRRTK ENLPFKDRIA DAYSDVMVTY TMTSSLYFIT FGMGASPFTN
IEAVKVFCQN MCVSILLNYF YIFSFFGSCL VFAGQLEQNR YHSIFCCKIP SAEYLDRKPV
WFQTVMSDGH QQTSHHETNP YQHHFIQHFL REHYNEWITN IYVKPFVVIL YLIYASFSFM
GCLQISDGAN IINLLASDSP SVSYAMVQQK YFSNYSPVIG FYVYEPLEYW NSSVQDDLRR
LCSGFTAVSW VEQYYQFLKV SNVSANNKSD FISVLQSSFL KKPEFQHFRN DIIFSKAGDE
SNIIASRLYL VARTSRDKQK EITEVLEKLR PLSLSKSIRF IVFNPSFVFM DHYSLSVTVP
VLIAGFGVLL VLILTFFLVI HPLGNFWLIL SVTSIELGVL GLMTLWNVDM DCISILCLIY
TLNFAIDHCA PLLFTFVLAT EHTRTQCIKS SLQDHGTAIL QNVTSFLIGL VPLLFVPSNL
TFTLFKCLLL TGGCTLLHCF VILPVFLTFF PPSKKHHKKK KRAKRKEREE IECIEIQENP
DHVTTV
