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Protein

Hedgehog-interacting protein

Gene

Hhip

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

GO - Biological processi

  • carbohydrate metabolic process Source: InterPro
  • dorsal/ventral pattern formation Source: MGI
  • epithelial tube branching involved in lung morphogenesis Source: MGI
  • negative regulation of angiogenesis Source: BHF-UCL
  • negative regulation of signal transduction Source: UniProtKB
  • negative regulation of smoothened signaling pathway Source: BHF-UCL
  • neuroblast proliferation Source: MGI
  • organ morphogenesis Source: MGI
  • regulation of fibroblast growth factor receptor signaling pathway Source: MGI
  • signal transduction Source: MGI
  • skeletal system morphogenesis Source: BHF-UCL
  • smoothened signaling pathway Source: MGI
Complete GO annotation...

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_295321. Ligand-receptor interactions.

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 Componenti: 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

  • cell surface Source: MGI
  • extracellular region Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: MGI
Complete GO annotation...

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

MaxQBiQ7TN16.
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.
GenevisibleiQ7TN16. MM.

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.
STRINGi10090.ENSMUSP00000078047.

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

        10         20         30         40         50
MLKMLSFKLL LLAVALGFFE GDAKFGERNE GSGARRRRCL NGNPPKRLKR
60 70 80 90 100
RDRRVMSQLE LLSGGEILCG GFYPRVSCCL QSDSPGLGRL ENKIFSATNN
110 120 130 140 150
SECSRLLEEI QCAPCSPHSQ SLFYTPERDV LDGDLALPLL CKDYCKEFFY
160 170 180 190 200
TCRGHIPGLL QTTADEFCFY YARKDAGLCF PDFPRKQVRG PASNYLGQME
210 220 230 240 250
DYEKVGGISR KHKHNCLCVQ EVMSGLRQPV SAVHSGDGSH RLFILEKEGY
260 270 280 290 300
VKILTPEGEL FKEPYLDIHK LVQSGIKGGD ERGLLSLAFH PNYKKNGKLY
310 320 330 340 350
VSYTTNQERW AIGPHDHILR VVEYTVSRKN PHQVDVRTAR VFLEVAELHR
360 370 380 390 400
KHLGGQLLFG PDGFLYIILG DGMITLDDME EMDGLSDFTG SVLRLDVDTD
410 420 430 440 450
MCNVPYSIPR SNPHFNSTNQ PPEVFAHGLH DPGRCAVDRH PTDININLTI
460 470 480 490 500
LCSDSNGKNR SSARILQIIK GRDYESEPSL LEFKPFSNGP LVGGFVYRGC
510 520 530 540 550
QSERLYGSYV FGDRNGNFLT LQQSPVTKQW QEKPLCLGAS SSCRGYFSGH
560 570 580 590 600
ILGFGEDELG EVYILSSSKS MTQTHNGKLY KIVDPKRPLM PEECRVTVQP
610 620 630 640 650
AQPLTSDCSR LCRNGYYTPT GKCCCSPGWE GDFCRIAKCE PACRHGGVCV
660 670 680 690 700
RPNKCLCKKG YLGPQCEQVD RNVRRVTRAG ILDQIIDMTS YLLDLTSYIV
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi200300. 1 interaction.
MINTiMINT-4997541.
STRINGi10090.ENSMUSP00000078047.

PTM databases

PhosphoSiteiQ7TN16.

Proteomic databases

MaxQBiQ7TN16.
PRIDEiQ7TN16.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi64399.
MGIiMGI:1341847. Hhip.

Phylogenomic databases

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

Enzyme and pathway databases

ReactomeiREACT_295321. Ligand-receptor interactions.

Miscellaneous databases

ChiTaRSiHhip. mouse.
NextBioi287849.
PROiQ7TN16.
SOURCEiSearch...

Gene expression databases

BgeeiQ7TN16.
CleanExiMM_HHIP.
GenevisibleiQ7TN16. MM.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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: June 24, 2015
This is version 102 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.