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Protein

Protein patched homolog 1

Gene

Ptch1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a receptor for sonic hedgehog (SHH), indian hedgehog (IHH) and desert hedgehog (DHH). Associates with the smoothened protein (SMO) to transduce the hedgehog's proteins signal. Seems to have a tumor suppressor function, as inactivation of this protein is probably a necessary, if not sufficient step for tumorigenesis.1 Publication

GO - Molecular functioni

  1. cholesterol binding Source: Roslin
  2. cyclin binding Source: BHF-UCL
  3. hedgehog family protein binding Source: MGI
  4. hedgehog receptor activity Source: MGI
  5. heparin binding Source: Roslin
  6. patched binding Source: Roslin
  7. protein complex binding Source: BHF-UCL
  8. smoothened binding Source: MGI
  9. zinc ion binding Source: Roslin

GO - Biological processi

  1. brain development Source: BHF-UCL
  2. branching involved in ureteric bud morphogenesis Source: MGI
  3. cell differentiation involved in kidney development Source: MGI
  4. cell fate determination Source: MGI
  5. cell proliferation involved in metanephros development Source: MGI
  6. cellular response to cholesterol Source: BHF-UCL
  7. dorsal/ventral neural tube patterning Source: MGI
  8. dorsal/ventral pattern formation Source: MGI
  9. embryonic limb morphogenesis Source: MGI
  10. embryonic organ development Source: MGI
  11. epidermal cell fate specification Source: MGI
  12. epidermis development Source: MGI
  13. glucose homeostasis Source: MGI
  14. heart morphogenesis Source: MGI
  15. hindlimb morphogenesis Source: MGI
  16. in utero embryonic development Source: MGI
  17. keratinocyte proliferation Source: MGI
  18. limb morphogenesis Source: MGI
  19. mammary gland development Source: MGI
  20. mammary gland duct morphogenesis Source: MGI
  21. mammary gland epithelial cell differentiation Source: MGI
  22. negative regulation of cell division Source: BHF-UCL
  23. negative regulation of cell proliferation Source: BHF-UCL
  24. negative regulation of epithelial cell proliferation Source: MGI
  25. negative regulation of multicellular organism growth Source: MGI
  26. negative regulation of osteoblast differentiation Source: MGI
  27. negative regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  28. negative regulation of smoothened signaling pathway Source: BHF-UCL
  29. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  30. neural plate axis specification Source: BHF-UCL
  31. neural tube closure Source: MGI
  32. neural tube formation Source: Roslin
  33. neural tube patterning Source: MGI
  34. organ morphogenesis Source: MGI
  35. pattern specification process Source: MGI
  36. pharyngeal system development Source: MGI
  37. positive regulation of cholesterol efflux Source: MGI
  38. positive regulation of epidermal cell differentiation Source: MGI
  39. protein processing Source: MGI
  40. protein targeting to plasma membrane Source: MGI
  41. regulation of cell proliferation Source: MGI
  42. regulation of growth Source: MGI
  43. regulation of mitotic cell cycle Source: MGI
  44. regulation of protein localization Source: BHF-UCL
  45. regulation of smoothened signaling pathway Source: MGI
  46. response to chlorate Source: MGI
  47. response to drug Source: Ensembl
  48. response to estradiol Source: Ensembl
  49. response to mechanical stimulus Source: Ensembl
  50. response to retinoic acid Source: Ensembl
  51. signal transduction Source: Roslin
  52. smoothened signaling pathway Source: MGI
  53. smoothened signaling pathway involved in dorsal/ventral neural tube patterning Source: MGI
  54. somite development Source: BHF-UCL
  55. spinal cord motor neuron differentiation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

ReactomeiREACT_278699. Hedgehog 'off' state.
REACT_295321. Ligand-receptor interactions.
REACT_335449. Class B/2 (Secretin family receptors).
REACT_351311. Hedgehog 'on' state.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein patched homolog 1
Short name:
PTC
Short name:
PTC1
Gene namesi
Name:Ptch1
Synonyms:Ptch
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:105373. Ptch1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8686CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei87 – 10721HelicalSequence AnalysisAdd
BLAST
Topological domaini108 – 422315ExtracellularSequence AnalysisAdd
BLAST
Transmembranei423 – 44321HelicalSequence AnalysisAdd
BLAST
Topological domaini444 – 45815CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei459 – 47921HelicalSequence AnalysisAdd
BLAST
Topological domaini480 – 4878ExtracellularSequence Analysis
Transmembranei488 – 50821HelicalSequence AnalysisAdd
BLAST
Topological domaini509 – 53325CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei534 – 55421HelicalSequence AnalysisAdd
BLAST
Topological domaini555 – 5639ExtracellularSequence Analysis
Transmembranei564 – 58421HelicalSequence AnalysisAdd
BLAST
Topological domaini585 – 734150CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei735 – 75521HelicalSequence AnalysisAdd
BLAST
Topological domaini756 – 1013258ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1014 – 103421HelicalSequence AnalysisAdd
BLAST
Topological domaini1035 – 10395CytoplasmicSequence Analysis
Transmembranei1040 – 106021HelicalSequence AnalysisAdd
BLAST
Topological domaini1061 – 10699ExtracellularSequence Analysis
Transmembranei1070 – 109021HelicalSequence AnalysisAdd
BLAST
Topological domaini1091 – 110717CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei1108 – 112821HelicalSequence AnalysisAdd
BLAST
Topological domaini1129 – 114012ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1141 – 116121HelicalSequence AnalysisAdd
BLAST
Topological domaini1162 – 1434273CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. axonal growth cone Source: Ensembl
  2. caveola Source: MGI
  3. dendritic growth cone Source: Ensembl
  4. extracellular region Source: Roslin
  5. Golgi apparatus Source: Ensembl
  6. integral component of plasma membrane Source: MGI
  7. intracellular membrane-bounded organelle Source: MGI
  8. midbody Source: UniProtKB
  9. perinuclear region of cytoplasm Source: MGI
  10. plasma membrane Source: BHF-UCL
  11. postsynaptic density Source: Ensembl
  12. primary cilium Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1413 – 14131K → R: Accumulates at the plasma membrane, increased half-life and increased CASP9-mediated cell death. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 14341434Protein patched homolog 1PRO_0000205965Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi127 – 1271N-linked (GlcNAc...)Sequence Analysis
Glycosylationi298 – 2981N-linked (GlcNAc...)Sequence Analysis
Glycosylationi335 – 3351N-linked (GlcNAc...)Sequence Analysis
Glycosylationi400 – 4001N-linked (GlcNAc...)Sequence Analysis
Glycosylationi861 – 8611N-linked (GlcNAc...)Sequence Analysis
Glycosylationi986 – 9861N-linked (GlcNAc...)Sequence Analysis
Cross-linki1413 – 1413Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication

Post-translational modificationi

Glycosylation is necessary for SHH binding.By similarity
In the absence of Hh ligands, ubiquitination by ITCH at Lys-1413 promotes endocytosis and both proteasomal and lysosomal degradation.1 Publication

Keywords - PTMi

Glycoprotein, Isopeptide bond, Ubl conjugation

Proteomic databases

PRIDEiQ61115.

PTM databases

PhosphoSiteiQ61115.

Expressioni

Developmental stagei

Expressed at low level at 7 dpc, higher level at 11 and 15 dpc, and persists at moderate levels at 17 dpc. In the developing embryo, PTC is first detected within the ventral neural tube and later in the somites and limb buds. Expression in the limb buds is restricted to the posterior ectoderm surrounding the zone of polarizing activity. In the adult, expression is seen in brain, lung, liver, kidney and ocular tissues; lower levels in heart, skeletal muscle, and testis.

Inductioni

Activated by Sonic hedgehog.

Gene expression databases

BgeeiQ61115.
CleanExiMM_PTCH1.
ExpressionAtlasiQ61115. baseline and differential.
GenevestigatoriQ61115.

Interactioni

Subunit structurei

Interacts with SNX17 (By similarity). Interacts with IHH.By similarity1 Publication

Protein-protein interaction databases

DIPiDIP-60268N.

Structurei

3D structure databases

ProteinModelPortaliQ61115.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini424 – 584161SSDPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the patched family.Curated
Contains 1 SSD (sterol-sensing) domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG313603.
GeneTreeiENSGT00760000119174.
HOGENOMiHOG000231331.
HOVERGENiHBG003801.
InParanoidiQ61115.
KOiK06225.
OMAiLQRPSYC.
OrthoDBiEOG7HMS06.
PhylomeDBiQ61115.
TreeFamiTF106489.

Family and domain databases

InterProiIPR003392. Patched.
IPR000731. SSD.
IPR004766. TM_rcpt_patched.
[Graphical view]
PfamiPF02460. Patched. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00918. 2A060602. 1 hit.
PROSITEiPS50156. SSD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q61115-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASAGNAAGA LGRQAGGGRR RRTGGPHRAA PDRDYLHRPS YCDAAFALEQ
60 70 80 90 100
ISKGKATGRK APLWLRAKFQ RLLFKLGCYI QKNCGKFLVV GLLIFGAFAV
110 120 130 140 150
GLKAANLETN VEELWVEVGG RVSRELNYTR QKIGEEAMFN PQLMIQTPKE
160 170 180 190 200
EGANVLTTEA LLQHLDSALQ ASRVHVYMYN RQWKLEHLCY KSGELITETG
210 220 230 240 250
YMDQIIEYLY PCLIITPLDC FWEGAKLQSG TAYLLGKPPL RWTNFDPLEF
260 270 280 290 300
LEELKKINYQ VDSWEEMLNK AEVGHGYMDR PCLNPADPDC PATAPNKNST
310 320 330 340 350
KPLDVALVLN GGCQGLSRKY MHWQEELIVG GTVKNATGKL VSAHALQTMF
360 370 380 390 400
QLMTPKQMYE HFRGYDYVSH INWNEDRAAA ILEAWQRTYV EVVHQSVAPN
410 420 430 440 450
STQKVLPFTT TTLDDILKSF SDVSVIRVAS GYLLMLAYAC LTMLRWDCSK
460 470 480 490 500
SQGAVGLAGV LLVALSVAAG LGLCSLIGIS FNAATTQVLP FLALGVGVDD
510 520 530 540 550
VFLLAHAFSE TGQNKRIPFE DRTGECLKRT GASVALTSIS NVTAFFMAAL
560 570 580 590 600
IPIPALRAFS LQAAVVVVFN FAMVLLIFPA ILSMDLYRRE DRRLDIFCCF
610 620 630 640 650
TSPCVSRVIQ VEPQAYTEPH SNTRYSPPPP YTSHSFAHET HITMQSTVQL
660 670 680 690 700
RTEYDPHTHV YYTTAEPRSE ISVQPVTVTQ DNLSCQSPES TSSTRDLLSQ
710 720 730 740 750
FSDSSLHCLE PPCTKWTLSS FAEKHYAPFL LKPKAKVVVI LLFLGLLGVS
760 770 780 790 800
LYGTTRVRDG LDLTDIVPRE TREYDFIAAQ FKYFSFYNMY IVTQKADYPN
810 820 830 840 850
IQHLLYDLHK SFSNVKYVML EENKQLPQMW LHYFRDWLQG LQDAFDSDWE
860 870 880 890 900
TGRIMPNNYK NGSDDGVLAY KLLVQTGSRD KPIDISQLTK QRLVDADGII
910 920 930 940 950
NPSAFYIYLT AWVSNDPVAY AASQANIRPH RPEWVHDKAD YMPETRLRIP
960 970 980 990 1000
AAEPIEYAQF PFYLNGLRDT SDFVEAIEKV RVICNNYTSL GLSSYPNGYP
1010 1020 1030 1040 1050
FLFWEQYISL RHWLLLSISV VLACTFLVCA VFLLNPWTAG IIVMVLALMT
1060 1070 1080 1090 1100
VELFGMMGLI GIKLSAVPVV ILIASVGIGV EFTVHVALAF LTAIGDKNHR
1110 1120 1130 1140 1150
AMLALEHMFA PVLDGAVSTL LGVLMLAGSE FDFIVRYFFA VLAILTVLGV
1160 1170 1180 1190 1200
LNGLVLLPVL LSFFGPCPEV SPANGLNRLP TPSPEPPPSV VRFAVPPGHT
1210 1220 1230 1240 1250
NNGSDSSDSE YSSQTTVSGI SEELRQYEAQ QGAGGPAHQV IVEATENPVF
1260 1270 1280 1290 1300
ARSTVVHPDS RHQPPLTPRQ QPHLDSGSLS PGRQGQQPRR DPPREGLRPP
1310 1320 1330 1340 1350
PYRPRRDAFE ISTEGHSGPS NRDRSGPRGA RSHNPRNPTS TAMGSSVPSY
1360 1370 1380 1390 1400
CQPITTVTAS ASVTVAVHPP PGPGRNPRGG PCPGYESYPE TDHGVFEDPH
1410 1420 1430
VPFHVRCERR DSKVEVIELQ DVECEERPWG SSSN
Length:1,434
Mass (Da):159,273
Last modified:November 1, 1996 - v1
Checksum:iA5E9189E633173D0
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U46155 mRNA. Translation: AAC98798.1.
CCDSiCCDS26592.1.
PIRiT30172.
RefSeqiNP_032983.1. NM_008957.2.
XP_006517222.1. XM_006517159.2.
UniGeneiMm.228798.
Mm.488634.

Genome annotation databases

EnsembliENSMUST00000021921; ENSMUSP00000021921; ENSMUSG00000021466.
GeneIDi19206.
KEGGimmu:19206.
UCSCiuc007qxv.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U46155 mRNA. Translation: AAC98798.1.
CCDSiCCDS26592.1.
PIRiT30172.
RefSeqiNP_032983.1. NM_008957.2.
XP_006517222.1. XM_006517159.2.
UniGeneiMm.228798.
Mm.488634.

3D structure databases

ProteinModelPortaliQ61115.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60268N.

PTM databases

PhosphoSiteiQ61115.

Proteomic databases

PRIDEiQ61115.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000021921; ENSMUSP00000021921; ENSMUSG00000021466.
GeneIDi19206.
KEGGimmu:19206.
UCSCiuc007qxv.1. mouse.

Organism-specific databases

CTDi5727.
MGIiMGI:105373. Ptch1.

Phylogenomic databases

eggNOGiNOG313603.
GeneTreeiENSGT00760000119174.
HOGENOMiHOG000231331.
HOVERGENiHBG003801.
InParanoidiQ61115.
KOiK06225.
OMAiLQRPSYC.
OrthoDBiEOG7HMS06.
PhylomeDBiQ61115.
TreeFamiTF106489.

Enzyme and pathway databases

ReactomeiREACT_278699. Hedgehog 'off' state.
REACT_295321. Ligand-receptor interactions.
REACT_335449. Class B/2 (Secretin family receptors).
REACT_351311. Hedgehog 'on' state.

Miscellaneous databases

ChiTaRSiPtch1. mouse.
NextBioi295938.
PROiQ61115.
SOURCEiSearch...

Gene expression databases

BgeeiQ61115.
CleanExiMM_PTCH1.
ExpressionAtlasiQ61115. baseline and differential.
GenevestigatoriQ61115.

Family and domain databases

InterProiIPR003392. Patched.
IPR000731. SSD.
IPR004766. TM_rcpt_patched.
[Graphical view]
PfamiPF02460. Patched. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00918. 2A060602. 1 hit.
PROSITEiPS50156. SSD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Conservation of the hedgehog/patched signaling pathway from flies to mice: induction of a mouse patched gene by Hedgehog."
    Goodrich L.V., Johnson R.L., Milenkovic L., McMahon J.A., Scott M.P.
    Genes Dev. 10:301-312(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Embryo.
  2. "Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels."
    Ma G., Yu J., Xiao Y., Chan D., Gao B., Hu J., He Y., Guo S., Zhou J., Zhang L., Gao L., Zhang W., Kang Y., Cheah K.S., Feng G., Guo X., Wang Y., Zhou C.Z., He L.
    Cell Res. 21:1343-1357(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH IHH.
  3. "Patched-1 proapoptotic activity is downregulated by modification of K1413 by the E3 ubiquitin-protein ligase Itchy homolog."
    Chen X.L., Chinchilla P., Fombonne J., Ho L., Guix C., Keen J.H., Mehlen P., Riobo N.A.
    Mol. Cell. Biol. 34:3855-3866(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: UBIQUITINATION AT LYS-1413, MUTAGENESIS OF LYS-1413.

Entry informationi

Entry nameiPTC1_MOUSE
AccessioniPrimary (citable) accession number: Q61115
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: April 1, 2015
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.