HHIP_MOUSE
ID HHIP_MOUSE Reviewed; 700 AA.
AC Q7TN16; Q8C0B0; Q9WU59;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Hedgehog-interacting protein;
DE Short=HHIP;
DE Short=HIP;
DE Flags: Precursor;
GN Name=Hhip; Synonyms=Hip;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH SHH; IHH
RP AND DHH, AND DEVELOPMENTAL STAGE.
RX PubMed=10050855; DOI=10.1038/17611;
RA Chuang P.-T., McMahon A.P.;
RT "Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-
RT binding protein.";
RL Nature 397:617-621(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Medulla oblongata;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic 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).
RN [4]
RP TISSUE SPECIFICITY, AND IDENTIFICATION OF SOLUBLE FORMS.
RX PubMed=15019948; DOI=10.1016/j.mcn.2003.10.024;
RA Coulombe J., Traiffort E., Loulier K., Faure H., Ruat M.;
RT "Hedgehog interacting protein in the mature brain: membrane-associated and
RT soluble forms.";
RL Mol. Cell. Neurosci. 25:323-333(2004).
CC -!- FUNCTION: Modulates hedgehog signaling in several cell types, including
CC brain and lung through direct interaction with members of the hedgehog
CC family. Soluble forms inhibit Shh-induced differentiation in the
CC fibroblast cell line C3H/10T1/2.
CC -!- SUBUNIT: Interacts with all three hedgehog family members, SHH, IHH and
CC DHH. {ECO:0000269|PubMed:10050855}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10050855};
CC Peripheral membrane protein {ECO:0000269|PubMed:10050855}. Secreted
CC {ECO:0000269|PubMed:10050855}. Note=The last 22 C-terminal amino acids
CC may participate in cell membrane attachment.
CC -!- TISSUE SPECIFICITY: In the adult brain, high expression found in the
CC ventral cochlear nucleus, medial habenula, indusium griseum and tenia
CC tecta. Some expression also in the caudate putamen, the nucleus
CC accumbens, the ventral pallidum and in the superficial layers of the
CC superior colliculus. {ECO:0000269|PubMed:15019948}.
CC -!- DEVELOPMENTAL STAGE: First detected at 8.75 dpc, in the ventral midline
CC of the neural tube and in the ventral medial somites. At 10.5 dpc,
CC expression in the notochord is maintained in the caudal region.
CC Expression is lost in the floor plate, but is retained in the ventral
CC half of the neural tube and in the sclerotome of the adjacent somites.
CC In the midbrain, expression confined to two lateral stripes adjacent to
CC the floor plate. Also expressed in the gut mesenchyme along the length
CC of the gastro-intestinal tract and in the mesenchyme of the posterior
CC half of the limb. Expressed in the underlying mesenchyme of the
CC epithelium of a number of tissues including lung, gut and whisker. Also
CC expressed in the perichondrium and in the androgen-producing
CC interstitial somatic cells of the developing testis.
CC {ECO:0000269|PubMed:10050855}.
CC -!- DOMAIN: A flexible loop interacts with the SHH zinc binding site and
CC contributes to zinc binding. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the HHIP family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF116865; AAD31172.1; -; mRNA.
DR EMBL; AK031841; BAC27575.1; -; mRNA.
DR EMBL; BC053012; AAH53012.1; -; mRNA.
DR CCDS; CCDS22440.1; -.
DR RefSeq; NP_064655.4; NM_020259.4.
DR AlphaFoldDB; Q7TN16; -.
DR SMR; Q7TN16; -.
DR BioGRID; 200300; 1.
DR STRING; 10090.ENSMUSP00000078047; -.
DR GlyGen; Q7TN16; 4 sites.
DR PhosphoSitePlus; Q7TN16; -.
DR MaxQB; Q7TN16; -.
DR PaxDb; Q7TN16; -.
DR PRIDE; Q7TN16; -.
DR ProteomicsDB; 269789; -.
DR Antibodypedia; 2783; 245 antibodies from 28 providers.
DR DNASU; 15245; -.
DR Ensembl; ENSMUST00000079038; ENSMUSP00000078047; ENSMUSG00000064325.
DR GeneID; 15245; -.
DR KEGG; mmu:15245; -.
DR UCSC; uc009mix.2; mouse.
DR CTD; 64399; -.
DR MGI; MGI:1341847; Hhip.
DR VEuPathDB; HostDB:ENSMUSG00000064325; -.
DR eggNOG; KOG4295; Eukaryota.
DR GeneTree; ENSGT00940000158660; -.
DR HOGENOM; CLU_012344_0_0_1; -.
DR InParanoid; Q7TN16; -.
DR OMA; NCFCVQE; -.
DR OrthoDB; 728630at2759; -.
DR PhylomeDB; Q7TN16; -.
DR TreeFam; TF329059; -.
DR Reactome; R-MMU-5632681; Ligand-receptor interactions.
DR BioGRID-ORCS; 15245; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Hhip; mouse.
DR PRO; PR:Q7TN16; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q7TN16; protein.
DR Bgee; ENSMUSG00000064325; Expressed in left lung lobe and 155 other tissues.
DR Genevisible; Q7TN16; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0097108; F:hedgehog family protein binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IGI:MGI.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IMP:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; NAS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0009968; P:negative regulation of signal transduction; ISS:UniProtKB.
DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IDA:BHF-UCL.
DR GO; GO:0007405; P:neuroblast proliferation; IGI:MGI.
DR GO; GO:0040036; P:regulation of fibroblast growth factor receptor signaling pathway; IMP:MGI.
DR GO; GO:0007165; P:signal transduction; IDA:MGI.
DR GO; GO:0048705; P:skeletal system morphogenesis; IMP: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 Cell membrane; Disulfide bond; EGF-like domain; Glycoprotein; Membrane;
KW Metal-binding; 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_0000007624"
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 /evidence="ECO:0000250"
FT BINDING 383
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="ligand shared with SHH"
FT /evidence="ECO:0000250"
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:0000255"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 216..536
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 218..543
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 402..624
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 435..452
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 500..594
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 612..623
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 625..634
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 639..649
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 643..655
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 657..666
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CONFLICT 29
FT /note="N -> S (in Ref. 1; AAD31172)"
FT /evidence="ECO:0000305"
FT CONFLICT 473
FT /note="D -> G (in Ref. 3; AAH53012)"
FT /evidence="ECO:0000305"
FT CONFLICT 607
FT /note="D -> V (in Ref. 2; BAC27575)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 700 AA; 78513 MW; 91007C5AF6070B80 CRC64;
MLKMLSFKLL LLAVALGFFE GDAKFGERNE GSGARRRRCL NGNPPKRLKR RDRRVMSQLE
LLSGGEILCG GFYPRVSCCL QSDSPGLGRL ENKIFSATNN SECSRLLEEI QCAPCSPHSQ
SLFYTPERDV LDGDLALPLL CKDYCKEFFY TCRGHIPGLL QTTADEFCFY YARKDAGLCF
PDFPRKQVRG PASNYLGQME DYEKVGGISR KHKHNCLCVQ EVMSGLRQPV SAVHSGDGSH
RLFILEKEGY VKILTPEGEL FKEPYLDIHK LVQSGIKGGD ERGLLSLAFH PNYKKNGKLY
VSYTTNQERW AIGPHDHILR VVEYTVSRKN PHQVDVRTAR VFLEVAELHR KHLGGQLLFG
PDGFLYIILG DGMITLDDME EMDGLSDFTG SVLRLDVDTD MCNVPYSIPR SNPHFNSTNQ
PPEVFAHGLH DPGRCAVDRH PTDININLTI LCSDSNGKNR SSARILQIIK GRDYESEPSL
LEFKPFSNGP LVGGFVYRGC QSERLYGSYV FGDRNGNFLT LQQSPVTKQW QEKPLCLGAS
SSCRGYFSGH ILGFGEDELG EVYILSSSKS MTQTHNGKLY KIVDPKRPLM PEECRVTVQP
AQPLTSDCSR LCRNGYYTPT GKCCCSPGWE GDFCRIAKCE PACRHGGVCV RPNKCLCKKG
YLGPQCEQVD RNVRRVTRAG ILDQIIDMTS YLLDLTSYIV
