GenomeNet

Database: UniProt
Entry: Q96QV1
LinkDB: Q96QV1
Original site: Q96QV1 
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   02-JUN-2021, entry version 158.
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   PDBsum; 2WFT; -.
DR   PDBsum; 2WFX; -.
DR   PDBsum; 2WG3; -.
DR   PDBsum; 2WG4; -.
DR   PDBsum; 3HO3; -.
DR   PDBsum; 3HO4; -.
DR   PDBsum; 3HO5; -.
DR   SMR; Q96QV1; -.
DR   BioGRID; 122156; 1.
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   PaxDb; Q96QV1; -.
DR   PeptideAtlas; Q96QV1; -.
DR   PRIDE; Q96QV1; -.
DR   ProteomicsDB; 77909; -. [Q96QV1-1]
DR   ProteomicsDB; 77910; -. [Q96QV1-2]
DR   Antibodypedia; 2783; 235 antibodies.
DR   DNASU; 64399; -.
DR   Ensembl; ENST00000296575; ENSP00000296575; ENSG00000164161. [Q96QV1-1]
DR   Ensembl; ENST00000434550; ENSP00000408587; ENSG00000164161. [Q96QV1-2]
DR   GeneID; 64399; -.
DR   KEGG; hsa:64399; -.
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:ENSG00000164161.9; -.
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; 6 hits in 983 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 172 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:0003824; F:catalytic activity; IEA:InterPro.
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   METAL           383
FT                   /note="Zinc; 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          217..233
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          236..239
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          242..246
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   TURN            247..249
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          250..254
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          256..258
FT                   /evidence="ECO:0007829|PDB:2WG4"
FT   STRAND          265..267
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   TURN            269..271
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          277..279
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          283..289
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   HELIX           293..296
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          298..305
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          312..315
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          317..326
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   HELIX           336..338
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          340..352
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          354..359
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   HELIX           361..363
FT                   /evidence="ECO:0007829|PDB:3HO5"
FT   STRAND          365..369
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   HELIX           376..381
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          391..396
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          402..405
FT                   /evidence="ECO:0007829|PDB:2WFT"
FT   TURN            413..416
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          418..420
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          424..427
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          430..432
FT                   /evidence="ECO:0007829|PDB:3HO3"
FT   STRAND          434..440
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          442..445
FT                   /evidence="ECO:0007829|PDB:2WG4"
FT   STRAND          447..453
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          457..459
FT                   /evidence="ECO:0007829|PDB:3HO3"
FT   STRAND          463..468
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          481..483
FT                   /evidence="ECO:0007829|PDB:3HO3"
FT   STRAND          491..496
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   TURN            503..507
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          509..513
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          514..516
FT                   /evidence="ECO:0007829|PDB:3HO3"
FT   STRAND          518..522
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          525..528
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          531..535
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          537..539
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          543..545
FT                   /evidence="ECO:0007829|PDB:2WFT"
FT   STRAND          549..556
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          558..560
FT                   /evidence="ECO:0007829|PDB:3HO3"
FT   STRAND          562..569
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   HELIX           571..573
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          575..583
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          587..590
FT                   /evidence="ECO:0007829|PDB:2WFT"
FT   HELIX           592..594
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   HELIX           607..611
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          614..617
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          623..625
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          629..631
FT                   /evidence="ECO:0007829|PDB:2WG3"
FT   STRAND          644..646
FT                   /evidence="ECO:0007829|PDB:2WFX"
FT   STRAND          648..651
FT                   /evidence="ECO:0007829|PDB:2WFT"
FT   STRAND          654..656
FT                   /evidence="ECO:0007829|PDB:2WFT"
FT   STRAND          661..663
FT                   /evidence="ECO:0007829|PDB:2WFT"
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
//
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