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Q7TN16

- HHIP_MOUSE

UniProt

Q7TN16 - HHIP_MOUSE

Protein

Hedgehog-interacting protein

Gene

Hhip

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 96 (01 Oct 2014)
      Sequence version 2 (29 Mar 2005)
      Previous versions | rss
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    Functioni

    Modulates hedgehog signaling in several cell types, including brain and lung through direct interaction with members of the hedgehog family. Soluble forms inhibit Shh-induced differentiation in the fibroblast cell line C3H/10T1/2.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi383 – 3831Zinc; shared with SHHBy similarity

    GO - Molecular functioni

    1. oxidoreductase activity, acting on the CH-OH group of donors, quinone or similar compound as acceptor Source: InterPro
    2. protein binding Source: MGI
    3. quinone binding Source: InterPro
    4. zinc ion binding Source: UniProtKB

    GO - Biological processi

    1. carbohydrate metabolic process Source: InterPro
    2. dorsal/ventral pattern formation Source: MGI
    3. epithelial tube branching involved in lung morphogenesis Source: MGI
    4. negative regulation of angiogenesis Source: BHF-UCL
    5. negative regulation of signal transduction Source: UniProtKB
    6. negative regulation of smoothened signaling pathway Source: BHF-UCL
    7. neuroblast proliferation Source: MGI
    8. organ morphogenesis Source: MGI
    9. regulation of fibroblast growth factor receptor signaling pathway Source: MGI
    10. signal transduction Source: MGI
    11. skeletal system morphogenesis Source: BHF-UCL
    12. smoothened signaling pathway Source: MGI

    Keywords - Ligandi

    Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Hedgehog-interacting protein
    Short name:
    HHIP
    Short name:
    HIP
    Gene namesi
    Name:Hhip
    Synonyms:Hip
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 8

    Organism-specific databases

    MGIiMGI:1341847. Hhip.

    Subcellular locationi

    Cell membrane 1 Publication; Peripheral membrane protein 1 Publication. Secreted 1 Publication
    Note: The last 22 C-terminal amino acids may participate in cell membrane attachment.

    GO - Cellular componenti

    1. cell surface Source: MGI
    2. extracellular region Source: UniProtKB-SubCell
    3. integral component of plasma membrane Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Membrane, Secreted

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1717Sequence AnalysisAdd
    BLAST
    Chaini18 – 700683Hedgehog-interacting proteinPRO_0000007624Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi99 – 991N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi216 ↔ 536PROSITE-ProRule annotation
    Disulfide bondi218 ↔ 543PROSITE-ProRule annotation
    Disulfide bondi402 ↔ 624PROSITE-ProRule annotation
    Glycosylationi416 – 4161N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi435 ↔ 452PROSITE-ProRule annotation
    Glycosylationi447 – 4471N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi459 – 4591N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi500 ↔ 594PROSITE-ProRule annotation
    Disulfide bondi612 ↔ 623PROSITE-ProRule annotation
    Disulfide bondi625 ↔ 634PROSITE-ProRule annotation
    Disulfide bondi639 ↔ 649PROSITE-ProRule annotation
    Disulfide bondi643 ↔ 655PROSITE-ProRule annotation
    Disulfide bondi657 ↔ 666PROSITE-ProRule annotation

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    PRIDEiQ7TN16.

    PTM databases

    PhosphoSiteiQ7TN16.

    Expressioni

    Tissue specificityi

    In the adult brain, high expression found in the ventral cochlear nucleus, medial habenula, indusium griseum and tenia tecta. Some expression also in the caudate putamen, the nucleus accumbens, the ventral pallidum and in the superficial layers of the surerior colliculus.1 Publication

    Developmental stagei

    First detected at 8.75 dpc, in the ventral midline of the neural tube and in the ventral medial somites. At 10.5 dpc, expression in the notochord is maintained in the caudal region. Expression is lost in the floor plate, but is retained in the ventral half of the neural tube and in the sclerotome of the adjacent somites. In the midbrain, expression confined to two lateral stripes adjacent to the floor plate. Also expressed in the gut mesenchyme along the length of the gastro-intestinal tract and in the mesenchyme of the posterior half of the limb. Expressed in the underlying mesenchyme of the epithelium of a number of tissues including lung, gut and whisker. Also expressed in the perichondrium and in the androgen-producing interstitial somatic cells of the developing testis.1 Publication

    Gene expression databases

    BgeeiQ7TN16.
    CleanExiMM_HHIP.
    GenevestigatoriQ7TN16.

    Interactioni

    Subunit structurei

    Interacts with all three hedgehog family members, SHH, IHH and DHH.1 Publication

    Protein-protein interaction databases

    BioGridi200300. 1 interaction.
    MINTiMINT-4997541.

    Structurei

    3D structure databases

    ProteinModelPortaliQ7TN16.
    SMRiQ7TN16. Positions 214-668.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini607 – 63428EGF-like 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini635 – 66733EGF-like 2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni376 – 38813Interaction with SHH zinc binding siteBy similarityAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi35 – 5420Arg-richAdd
    BLAST

    Domaini

    A flexible loop interacts with the SHH zinc binding site and contributes to zinc binding.By similarity

    Sequence similaritiesi

    Belongs to the HHIP family.Curated
    Contains 2 EGF-like domains.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Repeat, Signal

    Phylogenomic databases

    eggNOGiCOG2133.
    GeneTreeiENSGT00530000063250.
    HOGENOMiHOG000008644.
    HOVERGENiHBG051901.
    InParanoidiQ7TN16.
    KOiK06231.
    OMAiFGDRNGN.
    OrthoDBiEOG7CZK54.
    PhylomeDBiQ7TN16.
    TreeFamiTF329059.

    Family and domain databases

    Gene3Di2.120.10.30. 1 hit.
    InterProiIPR011042. 6-blade_b-propeller_TolB-like.
    IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR018143. Folate_rcpt-like.
    IPR012938. Glc/Sorbosone_DH.
    IPR011041. Quinoprot_gluc/sorb_DH.
    [Graphical view]
    PfamiPF03024. Folate_rec. 1 hit.
    PF07995. GSDH. 1 hit.
    [Graphical view]
    SMARTiSM00181. EGF. 2 hits.
    [Graphical view]
    SUPFAMiSSF50952. SSF50952. 1 hit.
    PROSITEiPS00022. EGF_1. 2 hits.
    PS01186. EGF_2. 2 hits.
    PS50026. EGF_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q7TN16-1 [UniParc]FASTAAdd to Basket

    « Hide

    MLKMLSFKLL LLAVALGFFE GDAKFGERNE GSGARRRRCL NGNPPKRLKR    50
    RDRRVMSQLE LLSGGEILCG GFYPRVSCCL QSDSPGLGRL ENKIFSATNN 100
    SECSRLLEEI QCAPCSPHSQ SLFYTPERDV LDGDLALPLL CKDYCKEFFY 150
    TCRGHIPGLL QTTADEFCFY YARKDAGLCF PDFPRKQVRG PASNYLGQME 200
    DYEKVGGISR KHKHNCLCVQ EVMSGLRQPV SAVHSGDGSH RLFILEKEGY 250
    VKILTPEGEL FKEPYLDIHK LVQSGIKGGD ERGLLSLAFH PNYKKNGKLY 300
    VSYTTNQERW AIGPHDHILR VVEYTVSRKN PHQVDVRTAR VFLEVAELHR 350
    KHLGGQLLFG PDGFLYIILG DGMITLDDME EMDGLSDFTG SVLRLDVDTD 400
    MCNVPYSIPR SNPHFNSTNQ PPEVFAHGLH DPGRCAVDRH PTDININLTI 450
    LCSDSNGKNR SSARILQIIK GRDYESEPSL LEFKPFSNGP LVGGFVYRGC 500
    QSERLYGSYV FGDRNGNFLT LQQSPVTKQW QEKPLCLGAS SSCRGYFSGH 550
    ILGFGEDELG EVYILSSSKS MTQTHNGKLY KIVDPKRPLM PEECRVTVQP 600
    AQPLTSDCSR LCRNGYYTPT GKCCCSPGWE GDFCRIAKCE PACRHGGVCV 650
    RPNKCLCKKG YLGPQCEQVD RNVRRVTRAG ILDQIIDMTS YLLDLTSYIV 700
    Length:700
    Mass (Da):78,513
    Last modified:March 29, 2005 - v2
    Checksum:i91007C5AF6070B80
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti29 – 291N → S in AAD31172. (PubMed:10050855)Curated
    Sequence conflicti473 – 4731D → G in AAH53012. (PubMed:15489334)Curated
    Sequence conflicti607 – 6071D → V in BAC27575. (PubMed:16141072)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF116865 mRNA. Translation: AAD31172.1.
    AK031841 mRNA. Translation: BAC27575.1.
    BC053012 mRNA. Translation: AAH53012.1.
    CCDSiCCDS22440.1.
    RefSeqiNP_064655.4. NM_020259.4.
    UniGeneiMm.254493.

    Genome annotation databases

    EnsembliENSMUST00000079038; ENSMUSP00000078047; ENSMUSG00000064325.
    GeneIDi15245.
    KEGGimmu:15245.
    UCSCiuc009mix.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF116865 mRNA. Translation: AAD31172.1 .
    AK031841 mRNA. Translation: BAC27575.1 .
    BC053012 mRNA. Translation: AAH53012.1 .
    CCDSi CCDS22440.1.
    RefSeqi NP_064655.4. NM_020259.4.
    UniGenei Mm.254493.

    3D structure databases

    ProteinModelPortali Q7TN16.
    SMRi Q7TN16. Positions 214-668.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 200300. 1 interaction.
    MINTi MINT-4997541.

    PTM databases

    PhosphoSitei Q7TN16.

    Proteomic databases

    PRIDEi Q7TN16.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000079038 ; ENSMUSP00000078047 ; ENSMUSG00000064325 .
    GeneIDi 15245.
    KEGGi mmu:15245.
    UCSCi uc009mix.2. mouse.

    Organism-specific databases

    CTDi 64399.
    MGIi MGI:1341847. Hhip.

    Phylogenomic databases

    eggNOGi COG2133.
    GeneTreei ENSGT00530000063250.
    HOGENOMi HOG000008644.
    HOVERGENi HBG051901.
    InParanoidi Q7TN16.
    KOi K06231.
    OMAi FGDRNGN.
    OrthoDBi EOG7CZK54.
    PhylomeDBi Q7TN16.
    TreeFami TF329059.

    Miscellaneous databases

    ChiTaRSi HHIP. mouse.
    NextBioi 287849.
    PROi Q7TN16.
    SOURCEi Search...

    Gene expression databases

    Bgeei Q7TN16.
    CleanExi MM_HHIP.
    Genevestigatori Q7TN16.

    Family and domain databases

    Gene3Di 2.120.10.30. 1 hit.
    InterProi IPR011042. 6-blade_b-propeller_TolB-like.
    IPR000742. EG-like_dom.
    IPR013032. EGF-like_CS.
    IPR018143. Folate_rcpt-like.
    IPR012938. Glc/Sorbosone_DH.
    IPR011041. Quinoprot_gluc/sorb_DH.
    [Graphical view ]
    Pfami PF03024. Folate_rec. 1 hit.
    PF07995. GSDH. 1 hit.
    [Graphical view ]
    SMARTi SM00181. EGF. 2 hits.
    [Graphical view ]
    SUPFAMi SSF50952. SSF50952. 1 hit.
    PROSITEi PS00022. EGF_1. 2 hits.
    PS01186. EGF_2. 2 hits.
    PS50026. EGF_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Vertebrate Hedgehog signalling modulated by induction of a Hedgehog-binding protein."
      Chuang P.-T., McMahon A.P.
      Nature 397:617-621(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, INTERACTION WITH SHH; IHH AND DHH, DEVELOPMENTAL STAGE.
    2. "The transcriptional landscape of the mammalian genome."
      Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
      , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J.
      Tissue: Medulla oblongata.
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6.
      Tissue: Embryonic brain.
    4. "Hedgehog interacting protein in the mature brain: membrane-associated and soluble forms."
      Coulombe J., Traiffort E., Loulier K., Faure H., Ruat M.
      Mol. Cell. Neurosci. 25:323-333(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY, IDENTIFICATION OF SOLUBLE FORMS.

    Entry informationi

    Entry nameiHHIP_MOUSE
    AccessioniPrimary (citable) accession number: Q7TN16
    Secondary accession number(s): Q8C0B0, Q9WU59
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 29, 2005
    Last sequence update: March 29, 2005
    Last modified: October 1, 2014
    This is version 96 of the entry and version 2 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