Q9Y6C5 (PTC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein patched homolog 2
Short name=PTC2

Gene names

Name:	PTCH2
ORF Names:	UNQ560/PRO1121/PRO57079

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1203 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	May have a role in epidermal development. May act as a receptor for Sonic hedgehog (SHH).
Subcellular location	Membrane; Multi-pass membrane protein.
Involvement in disease	Defects in PTCH2 are a cause of medulloblastoma (MDB) [MIM:155255]. MDB is a malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. Although the majority of medulloblastomas occur sporadically, some manifest within familial cancer syndromes such as Turcot syndrome and basal cell nevus syndrome (Gorlin syndrome). Ref.2 Defects in PTCH2 are a cause of sporadic basal cell carcinoma (BCC) [MIM:605462]. Ref.2
Sequence similarities	Belongs to the patched family. Contains 1 SSD (sterol-sensing) domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of smoothened signaling pathway Traceable author statement. Source: BHF-UCL
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	hedgehog family protein binding Inferred from physical interaction Ref.1. Source: BHF-UCL hedgehog receptor activity Traceable author statement. Source: BHF-UCL smoothened binding Inferred from physical interaction Ref.1. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9Y6C5-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9Y6C5-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1143-1203: WGASSSLPQSFARVTTSMTVAIHPPPLPGAYIHPAPDEPPWSPAATSSGNLSSRGPGPATG → PEEI

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1203	1203	Protein patched homolog 2		PRO_0000205970
Regions
	Topological domain	1 – 57	57	Cytoplasmic Potential
	Transmembrane	58 – 78	21	Helical; Potential
	Topological domain	79 – 392	314	Extracellular Potential
	Transmembrane	393 – 413	21	Helical; Potential
	Topological domain	414 – 428	15	Cytoplasmic Potential
	Transmembrane	429 – 449	21	Helical; Potential
	Topological domain	450 – 457	8	Extracellular Potential
	Transmembrane	458 – 478	21	Helical; Potential
	Topological domain	479 – 501	23	Cytoplasmic Potential
	Transmembrane	502 – 522	21	Helical; Potential
	Topological domain	523 – 531	9	Extracellular Potential
	Transmembrane	532 – 552	21	Helical; Potential
	Topological domain	553 – 686	134	Cytoplasmic Potential
	Transmembrane	687 – 707	21	Helical; Potential
	Topological domain	708 – 963	256	Extracellular Potential
	Transmembrane	964 – 984	21	Helical; Potential
	Topological domain	985 – 991	7	Cytoplasmic Potential
	Transmembrane	992 – 1012	21	Helical; Potential
	Topological domain	1013	1	Extracellular Potential
	Transmembrane	1014 – 1034	21	Helical; Potential
	Topological domain	1035 – 1064	30	Cytoplasmic Potential
	Transmembrane	1065 – 1085	21	Helical; Potential
	Topological domain	1086 – 1093	8	Extracellular Potential
	Transmembrane	1094 – 1114	21	Helical; Potential
	Topological domain	1115 – 1203	89	Cytoplasmic Potential
	Domain	394 – 552	159	SSD
Amino acid modifications
	Glycosylation	370	1	N-linked (GlcNAc...) Potential
	Glycosylation	812	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1143 – 1203	61	WGASS…GPATG → PEEI in isoform 2.		VSP_004542
	Natural variant	346	1	E → Q. Ref.5 Corresponds to variant rs11573578 [ dbSNP | Ensembl ].		VAR_018935
	Natural variant	493	1	E → K. Ref.5 Corresponds to variant rs11573581 [ dbSNP | Ensembl ].		VAR_018936
	Natural variant	622	1	H → Y. Ref.5 Corresponds to variant rs11573586 [ dbSNP | Ensembl ].		VAR_018937
	Natural variant	988	1	T → M. Ref.5 Corresponds to variant rs11573590 [ dbSNP | Ensembl ].		VAR_018938
	Natural variant	995	1	V → M. Corresponds to variant rs11573591 [ dbSNP | Ensembl ].		VAR_050466
	Natural variant	1019	1	V → M. Ref.5 Corresponds to variant rs11573591 [ dbSNP | Ensembl ].		VAR_018939
	Natural variant	1121	1	I → M. Ref.5 Corresponds to variant rs11573598 [ dbSNP | Ensembl ].		VAR_018940
Experimental info
	Sequence conflict	2	1	T → N in AAD25953. Ref.2
	Sequence conflict	120	1	R → L in AAD25953. Ref.2
	Sequence conflict	175	1	R → W in AAC79847. Ref.1
	Sequence conflict	175	1	R → W in AAQ88919. Ref.4
	Sequence conflict	175	1	R → W in AAQ89375. Ref.4
	Sequence conflict	753	1	Q → R in AAD25953. Ref.2
	Sequence conflict	787	1	N → S in AAD25953. Ref.2
	Sequence conflict	833	1	P → L in AAD17260. Ref.3
	Sequence conflict	837	1	S → G in AAD25953. Ref.2
	Sequence conflict	846	1	D → E in AAD25953. Ref.2
	Sequence conflict	897	1	L → F in AAD17260. Ref.3
	Sequence conflict	1203	1	G → GDYKDDDDK in AAQ88919. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 24, 2001. Version 2. Checksum: 4FAB06999782C031	FASTA	1,203	130,544
	10 20 30 40 50 60 MTRSPPLREL PPSYTPPART AAPQILAGSL KAPLWLRAYF QGLLFSLGCG IQRHCGKVLF 70 80 90 100 110 120 LGLLAFGALA LGLRMAIIET NLEQLWVEVG SRVSQELHYT KEKLGEEAAY TSQMLIQTAR 130 140 150 160 170 180 QEGENILTPE ALGLHLQAAL TASKVQVSLY GKSWDLNKIC YKSGVPLIEN GMIERMIEKL 190 200 210 220 230 240 FPCVILTPLD CFWEGAKLQG GSAYLPGRPD IQWTNLDPEQ LLEELGPFAS LEGFRELLDK 250 260 270 280 290 300 AQVGQAYVGR PCLHPDDLHC PPSAPNHHSR QAPNVAHELS GGCHGFSHKF MHWQEELLLG 310 320 330 340 350 360 GMARDPQGEL LRAEALQSTF LLMSPRQLYE HFRGDYQTHD IGWSEEQAST VLQAWQRRFV 370 380 390 400 410 420 QLAQEALPEN ASQQIHAFSS TTLDDILHAF SEVSAARVVG GYLLMLAYAC VTMLRWDCAQ 430 440 450 460 470 480 SQGSVGLAGV LLVALAVASG LGLCALLGIT FNAATTQVLP FLALGIGVDD VFLLAHAFTE 490 500 510 520 530 540 ALPGTPLQER MGECLQRTGT SVVLTSINNM AAFLMAALVP IPALRAFSLQ AAIVVGCTFV 550 560 570 580 590 600 AVMLVFPAIL SLDLRRRHCQ RLDVLCCFSS PCSAQVIQIL PQELGDGTVP VGIAHLTATV 610 620 630 640 650 660 QAFTHCEASS QHVVTILPPQ AHLVPPPSDP LGSELFSPGG STRDLLGQEE ETRQKAACKS 670 680 690 700 710 720 LPCARWNLAH FARYQFAPLL LQSHAKAIVL VLFGALLGLS LYGATLVQDG LALTDVVPRG 730 740 750 760 770 780 TKEHAFLSAQ LRYFSLYEVA LVTQGGFDYA HSQRALFDLH QRFSSLKAVL PPPATQAPRT 790 800 810 820 830 840 WLHYYRNWLQ GIQAAFDQDW ASGRITRHSY RNGSEDGALA YKLLIQTGDA QEPLDFSQLT 850 860 870 880 890 900 TRKLVDREGL IPPELFYMGL TVWVSSDPLG LAASQANFYP PPPEWLHDKY DTTGENLRIP 910 920 930 940 950 960 PAQPLEFAQF PFLLRGLQKT ADFVEAIEGA RAACAEAGQA GVHAYPSGSP FLFWEQYLGL 970 980 990 1000 1010 1020 RRCFLLAVCI LLVCTFLVCA LLLLNPWTAG LIVLVLAMMT VELFGIMGFL GIKLSAIPVV 1030 1040 1050 1060 1070 1080 ILVASVGIGV EFTVHVALGF LTTQGSRNLR AAHALEHTFA PVTDGAISTL LGLLMLAGSH 1090 1100 1110 1120 1130 1140 FDFIVRYFFA ALTVLTLLGL LHGLVLLPVL LSILGPPPEV IQMYKESPEI LSPPAPQGGG 1150 1160 1170 1180 1190 1200 LRWGASSSLP QSFARVTTSM TVAIHPPPLP GAYIHPAPDE PPWSPAATSS GNLSSRGPGP ATG
	Isoform 2 [UniParc]. Checksum: FC9A05E2E37C455F	FASTA	1,146	124,909
	10 20 30 40 50 60 MTRSPPLREL PPSYTPPART AAPQILAGSL KAPLWLRAYF QGLLFSLGCG IQRHCGKVLF 70 80 90 100 110 120 LGLLAFGALA LGLRMAIIET NLEQLWVEVG SRVSQELHYT KEKLGEEAAY TSQMLIQTAR 130 140 150 160 170 180 QEGENILTPE ALGLHLQAAL TASKVQVSLY GKSWDLNKIC YKSGVPLIEN GMIERMIEKL 190 200 210 220 230 240 FPCVILTPLD CFWEGAKLQG GSAYLPGRPD IQWTNLDPEQ LLEELGPFAS LEGFRELLDK 250 260 270 280 290 300 AQVGQAYVGR PCLHPDDLHC PPSAPNHHSR QAPNVAHELS GGCHGFSHKF MHWQEELLLG 310 320 330 340 350 360 GMARDPQGEL LRAEALQSTF LLMSPRQLYE HFRGDYQTHD IGWSEEQAST VLQAWQRRFV 370 380 390 400 410 420 QLAQEALPEN ASQQIHAFSS TTLDDILHAF SEVSAARVVG GYLLMLAYAC VTMLRWDCAQ 430 440 450 460 470 480 SQGSVGLAGV LLVALAVASG LGLCALLGIT FNAATTQVLP FLALGIGVDD VFLLAHAFTE 490 500 510 520 530 540 ALPGTPLQER MGECLQRTGT SVVLTSINNM AAFLMAALVP IPALRAFSLQ AAIVVGCTFV 550 560 570 580 590 600 AVMLVFPAIL SLDLRRRHCQ RLDVLCCFSS PCSAQVIQIL PQELGDGTVP VGIAHLTATV 610 620 630 640 650 660 QAFTHCEASS QHVVTILPPQ AHLVPPPSDP LGSELFSPGG STRDLLGQEE ETRQKAACKS 670 680 690 700 710 720 LPCARWNLAH FARYQFAPLL LQSHAKAIVL VLFGALLGLS LYGATLVQDG LALTDVVPRG 730 740 750 760 770 780 TKEHAFLSAQ LRYFSLYEVA LVTQGGFDYA HSQRALFDLH QRFSSLKAVL PPPATQAPRT 790 800 810 820 830 840 WLHYYRNWLQ GIQAAFDQDW ASGRITRHSY RNGSEDGALA YKLLIQTGDA QEPLDFSQLT 850 860 870 880 890 900 TRKLVDREGL IPPELFYMGL TVWVSSDPLG LAASQANFYP PPPEWLHDKY DTTGENLRIP 910 920 930 940 950 960 PAQPLEFAQF PFLLRGLQKT ADFVEAIEGA RAACAEAGQA GVHAYPSGSP FLFWEQYLGL 970 980 990 1000 1010 1020 RRCFLLAVCI LLVCTFLVCA LLLLNPWTAG LIVLVLAMMT VELFGIMGFL GIKLSAIPVV 1030 1040 1050 1060 1070 1080 ILVASVGIGV EFTVHVALGF LTTQGSRNLR AAHALEHTFA PVTDGAISTL LGLLMLAGSH 1090 1100 1110 1120 1130 1140 FDFIVRYFFA ALTVLTLLGL LHGLVLLPVL LSILGPPPEV IQMYKESPEI LSPPAPQGGG LRPEEI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of two patched receptors for the vertebrate hedgehog protein family." Carpenter D., Stone D.M., Brush J., Ryan A., Armanini M., Frantz G., Rosenthal A., de Sauvage F.J. Proc. Natl. Acad. Sci. U.S.A. 95:13630-13634(1998) [PubMed: 9811851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Isolation and characterization of human patched 2 (PTCH2), a putative tumour suppressor gene in basal cell carcinoma and medulloblastoma on chromosome 1p32." Smyth I., Narang M.A., Evans T., Heimann C., Nakamura Y., Chenevix-Trench G., Pietsch T., Wicking C., Wainwright B.J. Hum. Mol. Genet. 8:291-297(1999) [PubMed: 9931336] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INVOLVEMENT IN MDB AND BCC.
[3]	"PTCH2, a novel human patched gene, undergoing alternative splicing and up-regulated in basal cell carcinomas." Zaphiropoulos P.G., Unden A.B., Rahnama F., Hollingsworth R.E., Toftgard R. Cancer Res. 59:787-792(1999) [PubMed: 10029063] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[4]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	NIEHS SNPs program Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-346; LYS-493; TYR-622; MET-988; MET-1019 AND MET-1121.
[6]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF091501 mRNA. Translation: AAC79847.1. AF087651 mRNA. Translation: AAD25953.1. AF119569 mRNA. Translation: AAD17260.1. AY358555 mRNA. Translation: AAQ88919.1. AY359016 mRNA. Translation: AAQ89375.1. AY438664 Genomic DNA. Translation: AAR05447.1. AL136380, AL592166 Genomic DNA. Translation: CAI23127.1. AL592166, AL136380 Genomic DNA. Translation: CAI13000.1.
IPI	IPI00419647. IPI00471943.
RefSeq	NP_001159764.1. NM_001166292.1. NP_003729.3. NM_003738.4.
UniGene	Hs.591497.
3D structure databases
ProteinModelPortal	Q9Y6C5.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y6C5. 1 interaction.
STRING	Q9Y6C5.
PTM databases
PhosphoSite	Q9Y6C5.
Polymorphism databases
DMDM	12643356.
Proteomic databases
PRIDE	Q9Y6C5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000372192; ENSP00000361266; ENSG00000117425.
GeneID	8643.
KEGG	hsa:8643.
UCSC	uc001cms.1. human.
Organism-specific databases
CTD	8643.
GeneCards	GC01M045286.
H-InvDB	HIX0028541.
HGNC	HGNC:9586. PTCH2.
MIM	155255. phenotype. 603673. gene. 605462. phenotype.
neXtProt	NX_Q9Y6C5.
Orphanet	141276. Commissural facial cleft.
PharmGKB	PA33938.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG13554.
GeneTree	ENSGT00550000074234.
HOGENOM	HBG713504.
HOVERGEN	HBG003801.
InParanoid	Q9Y6C5.
OMA	SSQHVVT.
OrthoDB	EOG49CQ6V.
PhylomeDB	Q9Y6C5.
Enzyme and pathway databases
Pathway_Interaction_DB	hedgehog_2pathway. Signaling events mediated by the Hedgehog family.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q9Y6C5.
Bgee	Q9Y6C5.
CleanEx	HS_PTCH2.
Genevestigator	Q9Y6C5.
GermOnline	ENSG00000117425. Homo sapiens.
Family and domain databases
InterPro	IPR003392. Patched. IPR000731. SSD. IPR004766. TM_rcpt_patched. [Graphical view]
KO	K11101.
Pfam	PF02460. Patched. 1 hit. [Graphical view]
TIGRFAMs	TIGR00918. 2A060602. 1 hit.
PROSITE	PS50156. SSD. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	32403.
SOURCE	Search...

Entry information

Entry name

PTC2_HUMAN

Accession

Primary (citable) accession number: Q9Y6C5
Secondary accession number(s): O95341 , O95856, Q53Z57, Q5QP87, Q6UX14

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	January 24, 2001
Last modified:	January 25, 2012
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.