HHIP_HUMAN
ID HHIP_HUMAN Reviewed; 700 AA.
AC Q96QV1; Q6PK09; Q8NCI7; Q9BXK3; Q9H1J4; Q9H7E7;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 3.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Hedgehog-interacting protein;
DE Short=HHIP;
DE Short=HIP;
DE Flags: Precursor;
GN Name=HHIP; Synonyms=HIP; ORFNames=UNQ5825/PRO19644;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT ILE-341, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Fetal brain;
RA Huo L., Roessler E., Dutra A., Chuang P.-T., McMahon A.P., Muenke M.;
RT "Determination of the chromosomal location and genomic structure of the
RT Hedgehog-interacting protein gene, and analysis of its role in
RT holoprosencephaly.";
RL Gene Funct. Dis. 1:119-127(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=11435703; DOI=10.1159/000056918;
RA Bak M., Hansen C., Friis Henriksen K., Tommerup N.;
RT "The human hedgehog-interacting protein gene: structure and chromosome
RT mapping to 4q31.21-->q31.3.";
RL Cytogenet. Cell Genet. 92:300-303(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ILE-341.
RC TISSUE=Coronary arterial endothelium, and Teratocarcinoma;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Muscle;
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 [7]
RP FUNCTION, AND SUBUNIT.
RX PubMed=11472839; DOI=10.1016/s0925-4773(01)00427-0;
RA Pathi S., Pagan-Westphal S., Baker D.P., Garber E.A., Rayhorn P.,
RA Bumcrot D., Tabin C.J., Blake Pepinsky R., Williams K.P.;
RT "Comparative biological responses to human Sonic, Indian, and Desert
RT hedgehog.";
RL Mech. Dev. 106:107-117(2001).
RN [8]
RP POLYMORPHISM.
RX PubMed=18391950; DOI=10.1038/ng.125;
RA Lettre G., Jackson A.U., Gieger C., Schumacher F.R., Berndt S.I., Sanna S.,
RA Eyheramendy S., Voight B.F., Butler J.L., Guiducci C., Illig T.,
RA Hackett R., Heid I.M., Jacobs K.B., Lyssenko V., Uda M., Boehnke M.,
RA Chanock S.J., Groop L.C., Hu F.B., Isomaa B., Kraft P., Peltonen L.,
RA Salomaa V., Schlessinger D., Hunter D.J., Hayes R.B., Abecasis G.R.,
RA Wichmann H.-E., Mohlke K.L., Hirschhorn J.N.;
RT "Identification of ten loci associated with height highlights new
RT biological pathways in human growth.";
RL Nat. Genet. 40:584-591(2008).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 193-667 IN COMPLEX WITH SHH,
RP INTERACTION WITH SHH, FUNCTION, MUTAGENESIS OF GLU-380; MET-382; ASP-383
RP AND ASP-387, AND DISULFIDE BONDS.
RX PubMed=19561609; DOI=10.1038/nsmb.1632;
RA Bosanac I., Maun H.R., Scales S.J., Wen X., Lingel A., Bazan J.F.,
RA de Sauvage F.J., Hymowitz S.G., Lazarus R.A.;
RT "The structure of SHH in complex with HHIP reveals a recognition role for
RT the Shh pseudo active site in signaling.";
RL Nat. Struct. Mol. Biol. 16:691-697(2009).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 214-670 IN COMPLEX WITH SHH,
RP INTERACTION WITH SHH AND DHH, DISULFIDE BONDS, MUTAGENESIS OF ASP-383, AND
RP GLYCOSYLATION AT ASN-447.
RX PubMed=19561611; DOI=10.1038/nsmb.1607;
RA Bishop B., Aricescu A.R., Harlos K., O'Callaghan C.A., Jones E.Y.,
RA Siebold C.;
RT "Structural insights into hedgehog ligand sequestration by the human
RT hedgehog-interacting protein HHIP.";
RL Nat. Struct. Mol. Biol. 16:698-703(2009).
CC -!- FUNCTION: Modulates hedgehog signaling in several cell types including
CC brain and lung through direct interaction with members of the hedgehog
CC family. {ECO:0000269|PubMed:11472839, ECO:0000269|PubMed:19561609}.
CC -!- SUBUNIT: Interacts with all three hedgehog family members, SHH, IHH and
CC DHH. {ECO:0000269|PubMed:11472839, ECO:0000269|PubMed:19561609,
CC ECO:0000269|PubMed:19561611}.
CC -!- INTERACTION:
CC Q96QV1; Q15465: SHH; NbExp=10; IntAct=EBI-6598521, EBI-11666886;
CC Q96QV1-1; O43323: DHH; NbExp=4; IntAct=EBI-15791478, EBI-11667804;
CC Q96QV1-1; Q62226: Shh; Xeno; NbExp=4; IntAct=EBI-15791478, EBI-15610166;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Secreted {ECO:0000250}. Note=The last 22 C-
CC terminal amino acids may participate in cell membrane attachment.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96QV1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96QV1-2; Sequence=VSP_013192, VSP_013193;
CC -!- TISSUE SPECIFICITY: Widely expressed in fetal and adult tissues.
CC Highest expression in adult heart, liver and pancreas, and in fetal
CC kidney. {ECO:0000269|PubMed:11435703, ECO:0000269|Ref.1}.
CC -!- DOMAIN: A flexible loop interacts with the SHH zinc binding site and
CC contributes to zinc binding.
CC -!- POLYMORPHISM: Genetic variations in HHIP define the stature
CC quantitative trait locus 12 (STQTL12) [MIM:612224]. Adult height is an
CC easily observable and highly heritable complex continuous trait.
CC Because of this, it is a model trait for studying genetic influence on
CC quantitative traits. {ECO:0000269|PubMed:18391950}.
CC -!- MISCELLANEOUS: [Isoform 2]: Potentially soluble form. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the HHIP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14945.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY009951; AAG34731.1; -; mRNA.
DR EMBL; AF326471; AAK18182.1; -; Genomic_DNA.
DR EMBL; AF326459; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AF326460; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AF326462; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AF326464; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AF326466; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AF326468; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AF326470; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AF326469; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AF326467; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AF326465; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AF326463; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AF326461; AAK18182.1; JOINED; Genomic_DNA.
DR EMBL; AY009317; AAG35411.1; -; mRNA.
DR EMBL; AY358747; AAQ89107.1; -; mRNA.
DR EMBL; AK024645; BAB14945.1; ALT_INIT; mRNA.
DR EMBL; AK074711; BAC11154.1; -; mRNA.
DR EMBL; AC098588; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009298; AAH09298.1; -; mRNA.
DR EMBL; BC025311; AAH25311.1; -; mRNA.
DR CCDS; CCDS3762.1; -. [Q96QV1-1]
DR RefSeq; NP_071920.1; NM_022475.2. [Q96QV1-1]
DR PDB; 2WFT; X-ray; 2.80 A; A/B=214-671.
DR PDB; 2WFX; X-ray; 3.20 A; B=214-670.
DR PDB; 2WG3; X-ray; 2.60 A; C/D=214-670.
DR PDB; 2WG4; X-ray; 3.15 A; B=214-670.
DR PDB; 3HO3; X-ray; 2.90 A; A=193-667.
DR PDB; 3HO4; X-ray; 3.10 A; A/B=193-667.
DR PDB; 3HO5; X-ray; 3.01 A; A/B=193-667.
DR PDB; 7PGK; X-ray; 2.75 A; A=39-209.
DR PDB; 7PGL; X-ray; 2.63 A; A=39-209.
DR PDB; 7PGM; X-ray; 2.70 A; A/B/C=213-670.
DR PDB; 7PGN; X-ray; 2.40 A; A/B=213-670.
DR PDBsum; 2WFT; -.
DR PDBsum; 2WFX; -.
DR PDBsum; 2WG3; -.
DR PDBsum; 2WG4; -.
DR PDBsum; 3HO3; -.
DR PDBsum; 3HO4; -.
DR PDBsum; 3HO5; -.
DR PDBsum; 7PGK; -.
DR PDBsum; 7PGL; -.
DR PDBsum; 7PGM; -.
DR PDBsum; 7PGN; -.
DR AlphaFoldDB; Q96QV1; -.
DR SMR; Q96QV1; -.
DR BioGRID; 122156; 3.
DR DIP; DIP-48536N; -.
DR IntAct; Q96QV1; 6.
DR STRING; 9606.ENSP00000296575; -.
DR GlyGen; Q96QV1; 4 sites.
DR iPTMnet; Q96QV1; -.
DR PhosphoSitePlus; Q96QV1; -.
DR BioMuta; HHIP; -.
DR DMDM; 118572655; -.
DR EPD; Q96QV1; -.
DR MassIVE; Q96QV1; -.
DR MaxQB; Q96QV1; -.
DR PaxDb; Q96QV1; -.
DR PeptideAtlas; Q96QV1; -.
DR PRIDE; Q96QV1; -.
DR ProteomicsDB; 77909; -. [Q96QV1-1]
DR ProteomicsDB; 77910; -. [Q96QV1-2]
DR Antibodypedia; 2783; 245 antibodies from 28 providers.
DR DNASU; 64399; -.
DR Ensembl; ENST00000296575.8; ENSP00000296575.3; ENSG00000164161.10. [Q96QV1-1]
DR Ensembl; ENST00000434550.2; ENSP00000408587.2; ENSG00000164161.10. [Q96QV1-2]
DR GeneID; 64399; -.
DR KEGG; hsa:64399; -.
DR MANE-Select; ENST00000296575.8; ENSP00000296575.3; NM_022475.3; NP_071920.1.
DR UCSC; uc003ijr.3; human. [Q96QV1-1]
DR CTD; 64399; -.
DR DisGeNET; 64399; -.
DR GeneCards; HHIP; -.
DR HGNC; HGNC:14866; HHIP.
DR HPA; ENSG00000164161; Tissue enhanced (brain, lung).
DR MIM; 606178; gene.
DR MIM; 612224; phenotype.
DR neXtProt; NX_Q96QV1; -.
DR OpenTargets; ENSG00000164161; -.
DR PharmGKB; PA29276; -.
DR VEuPathDB; HostDB:ENSG00000164161; -.
DR eggNOG; KOG4295; Eukaryota.
DR GeneTree; ENSGT00940000158660; -.
DR HOGENOM; CLU_012344_0_0_1; -.
DR InParanoid; Q96QV1; -.
DR OMA; NCFCVQE; -.
DR OrthoDB; 728630at2759; -.
DR PhylomeDB; Q96QV1; -.
DR TreeFam; TF329059; -.
DR PathwayCommons; Q96QV1; -.
DR Reactome; R-HSA-5632681; Ligand-receptor interactions.
DR SignaLink; Q96QV1; -.
DR SIGNOR; Q96QV1; -.
DR BioGRID-ORCS; 64399; 14 hits in 1069 CRISPR screens.
DR ChiTaRS; HHIP; human.
DR EvolutionaryTrace; Q96QV1; -.
DR GeneWiki; HHIP; -.
DR GenomeRNAi; 64399; -.
DR Pharos; Q96QV1; Tbio.
DR PRO; PR:Q96QV1; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q96QV1; protein.
DR Bgee; ENSG00000164161; Expressed in corpus callosum and 144 other tissues.
DR Genevisible; Q96QV1; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0060170; C:ciliary membrane; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:BHF-UCL.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0097108; F:hedgehog family protein binding; IPI:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:Ensembl.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0009968; P:negative regulation of signal transduction; IDA:UniProtKB.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; ISS:BHF-UCL.
DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl.
DR GO; GO:0040036; P:regulation of fibroblast growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IEA:Ensembl.
DR GO; GO:0048705; P:skeletal system morphogenesis; ISS:BHF-UCL.
DR Gene3D; 2.120.10.30; -; 1.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR018143; Folate_rcpt-like.
DR InterPro; IPR012938; Glc/Sorbosone_DH.
DR InterPro; IPR011041; Quinoprot_gluc/sorb_DH.
DR Pfam; PF03024; Folate_rec; 1.
DR Pfam; PF07995; GSDH; 1.
DR SMART; SM00181; EGF; 2.
DR SUPFAM; SSF50952; SSF50952; 1.
DR PROSITE; PS00022; EGF_1; 2.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cytoplasm;
KW Disulfide bond; EGF-like domain; Glycoprotein; Membrane; Metal-binding;
KW Reference proteome; Repeat; Secreted; Signal; Zinc.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..700
FT /note="Hedgehog-interacting protein"
FT /id="PRO_0000007623"
FT DOMAIN 607..634
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 635..667
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REGION 376..388
FT /note="Interaction with SHH zinc binding site"
FT BINDING 383
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared with SHH"
FT CARBOHYD 99
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 416
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 447
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19561611"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 216..536
FT DISULFID 218..543
FT DISULFID 402..624
FT DISULFID 435..452
FT DISULFID 500..594
FT DISULFID 608..617
FT DISULFID 612..623
FT DISULFID 625..634
FT DISULFID 639..649
FT DISULFID 643..655
FT DISULFID 657..666
FT VAR_SEQ 278..320
FT /note="GGDERGLLSLAFHPNYKKNGKLYVSYTTNQERWAIGPHDHILR -> VGFLN
FT FIYFCAGYVNFILVLPSSLKVFLCNKRKNLAGENKGAT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_013192"
FT VAR_SEQ 321..700
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_013193"
FT VARIANT 341
FT /note="V -> I"
FT /evidence="ECO:0000269|PubMed:14702039, ECO:0000269|Ref.1"
FT /id="VAR_021518"
FT MUTAGEN 380
FT /note="E->A: Abolishes SHH binding."
FT /evidence="ECO:0000269|PubMed:19561609"
FT MUTAGEN 382
FT /note="M->A: Abolishes SHH binding."
FT /evidence="ECO:0000269|PubMed:19561609"
FT MUTAGEN 383
FT /note="D->A,R: Abolishes SHH binding."
FT /evidence="ECO:0000269|PubMed:19561609,
FT ECO:0000269|PubMed:19561611"
FT MUTAGEN 387
FT /note="D->A: Abolishes SHH binding."
FT /evidence="ECO:0000269|PubMed:19561609"
FT CONFLICT 126
FT /note="P -> L (in Ref. 4; BAC11154)"
FT /evidence="ECO:0000305"
FT CONFLICT 135
FT /note="L -> I (in Ref. 1; AAG34731)"
FT /evidence="ECO:0000305"
FT CONFLICT 173
FT /note="R -> G (in Ref. 4; BAC11154)"
FT /evidence="ECO:0000305"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:7PGL"
FT HELIX 50..57
FT /evidence="ECO:0007829|PDB:7PGK"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:7PGL"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:7PGL"
FT HELIX 102..111
FT /evidence="ECO:0007829|PDB:7PGL"
FT HELIX 112..115
FT /evidence="ECO:0007829|PDB:7PGL"
FT HELIX 119..122
FT /evidence="ECO:0007829|PDB:7PGL"
FT HELIX 142..152
FT /evidence="ECO:0007829|PDB:7PGL"
FT HELIX 159..161
FT /evidence="ECO:0007829|PDB:7PGL"
FT HELIX 164..171
FT /evidence="ECO:0007829|PDB:7PGL"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:7PGK"
FT STRAND 217..233
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 242..246
FT /evidence="ECO:0007829|PDB:7PGN"
FT TURN 247..249
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:2WG4"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:7PGN"
FT TURN 269..271
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 276..279
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:7PGN"
FT HELIX 293..296
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 298..305
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:2WG3"
FT STRAND 317..326
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 333..352
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 354..359
FT /evidence="ECO:0007829|PDB:7PGN"
FT HELIX 361..363
FT /evidence="ECO:0007829|PDB:3HO5"
FT STRAND 365..369
FT /evidence="ECO:0007829|PDB:7PGN"
FT HELIX 376..381
FT /evidence="ECO:0007829|PDB:7PGN"
FT TURN 387..390
FT /evidence="ECO:0007829|PDB:7PGM"
FT STRAND 391..396
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 402..405
FT /evidence="ECO:0007829|PDB:7PGN"
FT TURN 413..416
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 418..420
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 424..427
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 436..438
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 442..445
FT /evidence="ECO:0007829|PDB:2WG4"
FT STRAND 449..455
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 457..459
FT /evidence="ECO:0007829|PDB:3HO3"
FT STRAND 463..468
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 480..483
FT /evidence="ECO:0007829|PDB:7PGM"
FT STRAND 491..496
FT /evidence="ECO:0007829|PDB:7PGN"
FT TURN 504..507
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 509..513
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 514..516
FT /evidence="ECO:0007829|PDB:3HO3"
FT STRAND 518..523
FT /evidence="ECO:0007829|PDB:7PGN"
FT TURN 525..527
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 530..535
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 537..539
FT /evidence="ECO:0007829|PDB:2WG3"
FT STRAND 543..545
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 548..556
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 558..560
FT /evidence="ECO:0007829|PDB:3HO3"
FT STRAND 562..567
FT /evidence="ECO:0007829|PDB:7PGN"
FT HELIX 571..573
FT /evidence="ECO:0007829|PDB:2WG3"
FT STRAND 577..583
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 587..590
FT /evidence="ECO:0007829|PDB:7PGN"
FT HELIX 592..594
FT /evidence="ECO:0007829|PDB:7PGN"
FT HELIX 607..611
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 614..617
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 623..625
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 629..631
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 644..646
FT /evidence="ECO:0007829|PDB:2WFX"
FT STRAND 648..651
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 654..656
FT /evidence="ECO:0007829|PDB:7PGN"
FT STRAND 661..663
FT /evidence="ECO:0007829|PDB:7PGN"
SQ SEQUENCE 700 AA; 78851 MW; CC1CB3435E29303A CRC64;
MLKMLSFKLL LLAVALGFFE GDAKFGERNE GSGARRRRCL NGNPPKRLKR RDRRMMSQLE
LLSGGEMLCG GFYPRLSCCL RSDSPGLGRL ENKIFSVTNN TECGKLLEEI KCALCSPHSQ
SLFHSPEREV LERDLVLPLL CKDYCKEFFY TCRGHIPGFL QTTADEFCFY YARKDGGLCF
PDFPRKQVRG PASNYLDQME EYDKVEEISR KHKHNCFCIQ EVVSGLRQPV GALHSGDGSQ
RLFILEKEGY VKILTPEGEI FKEPYLDIHK LVQSGIKGGD ERGLLSLAFH PNYKKNGKLY
VSYTTNQERW AIGPHDHILR VVEYTVSRKN PHQVDLRTAR VFLEVAELHR KHLGGQLLFG
PDGFLYIILG DGMITLDDME EMDGLSDFTG SVLRLDVDTD MCNVPYSIPR SNPHFNSTNQ
PPEVFAHGLH DPGRCAVDRH PTDININLTI LCSDSNGKNR SSARILQIIK GKDYESEPSL
LEFKPFSNGP LVGGFVYRGC QSERLYGSYV FGDRNGNFLT LQQSPVTKQW QEKPLCLGTS
GSCRGYFSGH ILGFGEDELG EVYILSSSKS MTQTHNGKLY KIVDPKRPLM PEECRATVQP
AQTLTSECSR LCRNGYCTPT GKCCCSPGWE GDFCRTAKCE PACRHGGVCV RPNKCLCKKG
YLGPQCEQVD RNIRRVTRAG ILDQIIDMTS YLLDLTSYIV
