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Q7TN16 (HHIP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hedgehog-interacting protein

Short name=HHIP
Short name=HIP
Gene names
Name:Hhip
Synonyms:Hip
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length700 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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

Subcellular location

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

Tissue specificity

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. Ref.4

Developmental stage

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. Ref.1

Domain

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

Sequence similarities

Belongs to the HHIP family.

Contains 2 EGF-like domains.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   DomainEGF-like domain
Repeat
Signal
   LigandMetal-binding
Zinc
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcarbohydrate metabolic process

Inferred from electronic annotation. Source: InterPro

dorsal/ventral pattern formation

Inferred from genetic interaction PubMed 15576403. Source: MGI

epithelial tube branching involved in lung morphogenesis

Inferred from mutant phenotype PubMed 12569124. Source: MGI

negative regulation of angiogenesis

Non-traceable author statement PubMed 15294024. Source: BHF-UCL

negative regulation of signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of smoothened signaling pathway

Inferred from direct assay PubMed 15294024. Source: BHF-UCL

neuroblast proliferation

Inferred from genetic interaction PubMed 15576403. Source: MGI

organ morphogenesis

Inferred from mutant phenotype PubMed 12917290. Source: MGI

regulation of fibroblast growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 12569124. Source: MGI

signal transduction

Inferred from direct assay Ref.1. Source: MGI

skeletal system morphogenesis

Inferred from mutant phenotype Ref.1. Source: BHF-UCL

smoothened signaling pathway

Inferred from mutant phenotype PubMed 12569124. Source: MGI

   Cellular_componentcell surface

Inferred from direct assay PubMed 15576403. Source: MGI

extracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from direct assay Ref.1. Source: MGI

   Molecular_functionoxidoreductase activity, acting on the CH-OH group of donors, quinone or similar compound as acceptor

Inferred from electronic annotation. Source: InterPro

quinone binding

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1717 Potential
Chain18 – 700683Hedgehog-interacting protein
PRO_0000007624

Regions

Domain607 – 63428EGF-like 1
Domain635 – 66733EGF-like 2
Region376 – 38813Interaction with SHH zinc binding site By similarity
Compositional bias35 – 5420Arg-rich

Sites

Metal binding3831Zinc; shared with SHH By similarity

Amino acid modifications

Glycosylation991N-linked (GlcNAc...) Potential
Glycosylation4161N-linked (GlcNAc...) Potential
Glycosylation4471N-linked (GlcNAc...) Potential
Glycosylation4591N-linked (GlcNAc...) Potential
Disulfide bond216 ↔ 536 By similarity
Disulfide bond218 ↔ 543 By similarity
Disulfide bond402 ↔ 624 By similarity
Disulfide bond435 ↔ 452 By similarity
Disulfide bond500 ↔ 594 By similarity
Disulfide bond612 ↔ 623 By similarity
Disulfide bond625 ↔ 634 By similarity
Disulfide bond639 ↔ 649 By similarity
Disulfide bond643 ↔ 655 By similarity
Disulfide bond657 ↔ 666 By similarity

Experimental info

Sequence conflict291N → S in AAD31172. Ref.1
Sequence conflict4731D → G in AAH53012. Ref.3
Sequence conflict6071D → V in BAC27575. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q7TN16 [UniParc].

Last modified March 29, 2005. Version 2.
Checksum: 91007C5AF6070B80

FASTA70078,513
        10         20         30         40         50         60 
MLKMLSFKLL LLAVALGFFE GDAKFGERNE GSGARRRRCL NGNPPKRLKR RDRRVMSQLE 

        70         80         90        100        110        120 
LLSGGEILCG GFYPRVSCCL QSDSPGLGRL ENKIFSATNN SECSRLLEEI QCAPCSPHSQ 

       130        140        150        160        170        180 
SLFYTPERDV LDGDLALPLL CKDYCKEFFY TCRGHIPGLL QTTADEFCFY YARKDAGLCF 

       190        200        210        220        230        240 
PDFPRKQVRG PASNYLGQME DYEKVGGISR KHKHNCLCVQ EVMSGLRQPV SAVHSGDGSH 

       250        260        270        280        290        300 
RLFILEKEGY VKILTPEGEL FKEPYLDIHK LVQSGIKGGD ERGLLSLAFH PNYKKNGKLY 

       310        320        330        340        350        360 
VSYTTNQERW AIGPHDHILR VVEYTVSRKN PHQVDVRTAR VFLEVAELHR KHLGGQLLFG 

       370        380        390        400        410        420 
PDGFLYIILG DGMITLDDME EMDGLSDFTG SVLRLDVDTD MCNVPYSIPR SNPHFNSTNQ 

       430        440        450        460        470        480 
PPEVFAHGLH DPGRCAVDRH PTDININLTI LCSDSNGKNR SSARILQIIK GRDYESEPSL 

       490        500        510        520        530        540 
LEFKPFSNGP LVGGFVYRGC QSERLYGSYV FGDRNGNFLT LQQSPVTKQW QEKPLCLGAS 

       550        560        570        580        590        600 
SSCRGYFSGH ILGFGEDELG EVYILSSSKS MTQTHNGKLY KIVDPKRPLM PEECRVTVQP 

       610        620        630        640        650        660 
AQPLTSDCSR LCRNGYYTPT GKCCCSPGWE GDFCRIAKCE PACRHGGVCV RPNKCLCKKG 

       670        680        690        700 
YLGPQCEQVD RNVRRVTRAG ILDQIIDMTS YLLDLTSYIV 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF116865 mRNA. Translation: AAD31172.1.
AK031841 mRNA. Translation: BAC27575.1.
BC053012 mRNA. Translation: AAH53012.1.
RefSeqNP_064655.4. NM_020259.4.
UniGeneMm.254493.

3D structure databases

ProteinModelPortalQ7TN16.
SMRQ7TN16. Positions 68-156, 214-668.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200300. 1 interaction.
MINTMINT-4997541.

PTM databases

PhosphoSiteQ7TN16.

Proteomic databases

PRIDEQ7TN16.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000079038; ENSMUSP00000078047; ENSMUSG00000064325.
GeneID15245.
KEGGmmu:15245.
UCSCuc009mix.2. mouse.

Organism-specific databases

CTD64399.
MGIMGI:1341847. Hhip.

Phylogenomic databases

eggNOGCOG2133.
GeneTreeENSGT00530000063250.
HOGENOMHOG000008644.
HOVERGENHBG051901.
InParanoidQ7TN16.
KOK06231.
OMAFGDRNGN.
OrthoDBEOG7CZK54.
PhylomeDBQ7TN16.
TreeFamTF329059.

Gene expression databases

BgeeQ7TN16.
CleanExMM_HHIP.
GenevestigatorQ7TN16.

Family and domain databases

Gene3D2.120.10.30. 1 hit.
InterProIPR011042. 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]
PfamPF03024. Folate_rec. 1 hit.
PF07995. GSDH. 1 hit.
[Graphical view]
SMARTSM00181. EGF. 2 hits.
[Graphical view]
SUPFAMSSF50952. SSF50952. 1 hit.
PROSITEPS00022. EGF_1. 2 hits.
PS01186. EGF_2. 2 hits.
PS50026. EGF_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHHIP. mouse.
NextBio287849.
PROQ7TN16.
SOURCESearch...

Entry information

Entry nameHHIP_MOUSE
AccessionPrimary (citable) accession number: Q7TN16
Secondary accession number(s): Q8C0B0, Q9WU59
Entry history
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: March 29, 2005
Last modified: April 16, 2014
This is version 93 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot