Q7TN16 (HHIP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hedgehog-interacting protein
Short name=HHIP
Short name=HIP

Gene names

Name:	Hhip
Synonyms:	Hip

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	700 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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, C3H10T1/2.
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 component	Cell membrane Membrane Secreted
Domain	EGF-like domain Repeat Signal
Ligand	Metal-binding Zinc
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	dorsal/ventral pattern formation Inferred from genetic interaction. Source: MGI epithelial tube branching involved in lung morphogenesis Inferred from mutant phenotype. Source: MGI negative regulation of angiogenesis Non-traceable author statement. Source: BHF-UCL negative regulation of smoothened signaling pathway Inferred from direct assay. Source: BHF-UCL neuroblast proliferation Inferred from genetic interaction. Source: MGI regulation of fibroblast growth factor receptor signaling pathway Inferred from mutant phenotype. Source: MGI skeletal system morphogenesis Inferred from mutant phenotype Ref.1. Source: BHF-UCL smoothened signaling pathway Inferred from mutant phenotype. Source: MGI
Cellular component	cell surface Inferred from direct assay. Source: MGI extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Inferred from direct assay Ref.1. Source: MGI
Molecular function	catalytic activity Inferred from electronic annotation. Source: InterPro protein binding Inferred from physical interaction Ref.1. Source: MGI zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 17	17	Potential
	Chain	18 – 700	683	Hedgehog-interacting protein		PRO_0000007624
Regions
	Domain	607 – 634	28	EGF-like 1
	Domain	635 – 667	33	EGF-like 2
	Region	376 – 388	13	Interaction with SHH zinc binding site By similarity
	Compositional bias	35 – 54	20	Arg-rich
Sites
	Metal binding	383	1	Zinc; shared with SHH By similarity
Amino acid modifications
	Glycosylation	99	1	N-linked (GlcNAc...) Potential
	Glycosylation	416	1	N-linked (GlcNAc...) Potential
	Glycosylation	447	1	N-linked (GlcNAc...) Potential
	Glycosylation	459	1	N-linked (GlcNAc...) Potential
	Disulfide bond	216 ↔ 536		By similarity
	Disulfide bond	218 ↔ 543		By similarity
	Disulfide bond	402 ↔ 624		By similarity
	Disulfide bond	435 ↔ 452		By similarity
	Disulfide bond	500 ↔ 594		By similarity
	Disulfide bond	612 ↔ 623		By similarity
	Disulfide bond	625 ↔ 634		By similarity
	Disulfide bond	639 ↔ 649		By similarity
	Disulfide bond	643 ↔ 655		By similarity
	Disulfide bond	657 ↔ 666		By similarity
Experimental info
	Sequence conflict	29	1	N → S in AAD31172. Ref.1
	Sequence conflict	473	1	D → G in AAH53012. Ref.3
	Sequence conflict	607	1	D → V in BAC27575. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q7TN16 [UniParc]. Last modified March 29, 2005. Version 2. Checksum: 91007C5AF6070B80	FASTA	700	78,513
	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

References

	« Hide 'large scale' referencesShow '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: 10050855] [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: 16141072] [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: 15489334] [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: 15019948] [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.
IPI	IPI00458326.
RefSeq	NP_064655.4. NM_020259.4.
UniGene	Mm.254493.
3D structure databases
ProteinModelPortal	Q7TN16.
SMR	Q7TN16. Positions 214-668.
ModBase	Search...
Protein-protein interaction databases
STRING	Q7TN16.
PTM databases
PhosphoSite	Q7TN16.
Proteomic databases
PRIDE	Q7TN16.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000079038; ENSMUSP00000078047; ENSMUSG00000064325.
GeneID	15245.
KEGG	mmu:15245.
NMPDR	fig|10090.3.peg.18804.
UCSC	uc009mix.2. mouse.
Organism-specific databases
CTD	64399.
MGI	MGI:1341847. Hhip.
Phylogenomic databases
eggNOG	roNOG12529.
GeneTree	ENSGT00530000063250.
HOGENOM	HBG403054.
HOVERGEN	HBG051901.
InParanoid	Q7TN16.
OMA	NGNFLTL.
OrthoDB	EOG483D41.
PhylomeDB	Q7TN16.
Gene expression databases
ArrayExpress	Q7TN16.
Bgee	Q7TN16.
CleanEx	MM_HHIP.
Genevestigator	Q7TN16.
GermOnline	ENSMUSG00000064325. Mus musculus.
Family and domain databases
InterPro	IPR011042. 6-blade_b-propeller_TolB-like. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR018143. Folate_rcpt-like. IPR011041. Quinoprot_gluc/sorb_DH. [Graphical view]
Gene3D	G3DSA:2.120.10.30. 6-blade_b-propeller_TolB-like. 1 hit.
KO	K06231.
Pfam	PF03024. Folate_rec. 1 hit. [Graphical view]
SMART	SM00181. EGF. 2 hits. [Graphical view]
SUPFAM	SSF50952. Quino_gluc_DH. 1 hit.
PROSITE	PS00022. EGF_1. 2 hits. PS01186. EGF_2. 2 hits. PS50026. EGF_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	287849.
SOURCE	Search...

Entry information

Entry name

HHIP_MOUSE

Accession

Primary (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:	November 16, 2011
This is version 76 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program