Reviewed, UniProtKB/Swiss-Prot Q96QV1 (HHIP_HUMAN)

Names and origin

Protein names

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

Gene names

Name:	HHIP
Synonyms:	HIP
ORF Names:	UNQ5825/PRO19644

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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 transcript 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.
Subunit structure	Interacts with all three hedgehog family members, SHH, IHH and DHH By similarity.
Subcellular location	Cell membrane; Peripheral membrane protein By similarity. Secreted By similarity. Note: The last 22 C-terminal amino acids may participate in cell membrane attachment. Isoform 2: Cytoplasm Probable.
Tissue specificity	Widely expressed in fetal and adult tissues. Highest expression in adult heart, liver and pancreas, and in fetal kidney. Ref.1 Ref.2
Domain	The 6 Cys residues of the EGF-like domain are arranged in a disulfide pattern different from the one found in the canonical EGFs. The function of this domain is unclear. It may be a binding site for other proteins or the docking site for a putative alliinase receptor By similarity.
Polymorphism	Genetic variations in HHIP influences stature as a quantitative trait type 12 (STQTL12) [MIM:612226]. Adult height is an easily observable and highly heritable complex continuous trait. Because of this, it is a model trait for studying genetic influence on quantitative traits.
Sequence similarities	Belongs to the HHIP family. Contains 2 EGF-like domains.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	EGF-like domain Repeat Signal
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	catalytic activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q96QV1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q96QV1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     278-320: GGDERGLLSL...AIGPHDHILR → VGFLNFIYFC...NLAGENKGAT
     321-700: Missing.

Note: Potentially soluble form. No experimental confirmation available.

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_0000007623
Regions
	Domain	607 – 634	28	EGF-like 1
	Domain	635 – 667	33	EGF-like 2
	Compositional bias	35 – 54	20	Arg-rich
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	608 ↔ 623		By similarity
	Disulfide bond	612 ↔ 624		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
Natural variations
	Alternative sequence	278 – 320	43	GGDER…DHILR → VGFLNFIYFCAGYVNFILVL PSSLKVFLCNKRKNLAGENK GAT in isoform 2.		VSP_013192
	Alternative sequence	321 – 700	380	Missing in isoform 2.		VSP_013193
	Natural variant	341	1	V → I Ref.1 Ref.4		VAR_021518
Experimental info
	Sequence conflict	126	1	P → L in BAC11154. Ref.4
	Sequence conflict	135	1	L → I in AAG34731. Ref.1
	Sequence conflict	173	1	R → G in BAC11154. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 28, 2006. Version 3. Checksum: CC1CB3435E29303A	FASTA	700	78,851
	10 20 30 40 50 60 MLKMLSFKLL LLAVALGFFE GDAKFGERNE GSGARRRRCL NGNPPKRLKR RDRRMMSQLE 70 80 90 100 110 120 LLSGGEMLCG GFYPRLSCCL RSDSPGLGRL ENKIFSVTNN TECGKLLEEI KCALCSPHSQ 130 140 150 160 170 180 SLFHSPEREV LERDLVLPLL CKDYCKEFFY TCRGHIPGFL QTTADEFCFY YARKDGGLCF 190 200 210 220 230 240 PDFPRKQVRG PASNYLDQME EYDKVEEISR KHKHNCFCIQ EVVSGLRQPV GALHSGDGSQ 250 260 270 280 290 300 RLFILEKEGY VKILTPEGEI FKEPYLDIHK LVQSGIKGGD ERGLLSLAFH PNYKKNGKLY 310 320 330 340 350 360 VSYTTNQERW AIGPHDHILR VVEYTVSRKN PHQVDLRTAR 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 GKDYESEPSL 490 500 510 520 530 540 LEFKPFSNGP LVGGFVYRGC QSERLYGSYV FGDRNGNFLT LQQSPVTKQW QEKPLCLGTS 550 560 570 580 590 600 GSCRGYFSGH ILGFGEDELG EVYILSSSKS MTQTHNGKLY KIVDPKRPLM PEECRATVQP 610 620 630 640 650 660 AQTLTSECSR LCRNGYCTPT GKCCCSPGWE GDFCRTAKCE PACRHGGVCV RPNKCLCKKG 670 680 690 700 YLGPQCEQVD RNIRRVTRAG ILDQIIDMTS YLLDLTSYIV
	Isoform 2. Checksum: 3AF86509A46A7676	FASTA	320	36,373
	10 20 30 40 50 60 MLKMLSFKLL LLAVALGFFE GDAKFGERNE GSGARRRRCL NGNPPKRLKR RDRRMMSQLE 70 80 90 100 110 120 LLSGGEMLCG GFYPRLSCCL RSDSPGLGRL ENKIFSVTNN TECGKLLEEI KCALCSPHSQ 130 140 150 160 170 180 SLFHSPEREV LERDLVLPLL CKDYCKEFFY TCRGHIPGFL QTTADEFCFY YARKDGGLCF 190 200 210 220 230 240 PDFPRKQVRG PASNYLDQME EYDKVEEISR KHKHNCFCIQ EVVSGLRQPV GALHSGDGSQ 250 260 270 280 290 300 RLFILEKEGY VKILTPEGEI FKEPYLDIHK LVQSGIKVGF LNFIYFCAGY VNFILVLPSS 310 320 LKVFLCNKRK NLAGENKGAT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Determination of the chromosomal location and genomic structure of the Hedgehog-interacting protein gene, and analysis of its role in holoprosencephaly." Huo L., Roessler E., Dutra A., Chuang P.-T., McMahon A.P., Muenke M. Gene Funct. Dis. 1:119-127(2000) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), VARIANT ILE-341, TISSUE SPECIFICITY. Tissue: Fetal brain.
[2]	"The human hedgehog-interacting protein gene: structure and chromosome mapping to 4q31.21-->q31.3." Bak M., Hansen C., Friis Henriksen K., Tommerup N. Cytogenet. Cell Genet. 92:300-303(2001) [PubMed: 11435703] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY. Tissue: Testis.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ILE-341. Tissue: Coronary arterial endothelium and Teratocarcinoma.
[5]	"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] (ISOFORMS 1 AND 2). Tissue: Muscle.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AY009951 mRNA. Translation: AAG34731.1. AF326471 , AF326459, AF326460, AF326462, AF326464, AF326466, AF326468, AF326470, AF326469, AF326467, AF326465, AF326463, AF326461 Genomic DNA. Translation: AAK18182.1. AY009317 mRNA. Translation: AAG35411.1. AY358747 mRNA. Translation: AAQ89107.1. AK024645 mRNA. Translation: BAB14945.1. Different initiation. AK074711 mRNA. Translation: BAC11154.1. BC009298 mRNA. Translation: AAH09298.1. BC025311 mRNA. Translation: AAH25311.1.
IPI	IPI00045106. IPI00556597.
RefSeq	NP_071920.1.
UniGene	Hs.507991
3D structure databases
ModBase	Search...
PTM databases
PhosphoSite	Q96QV1.
Proteomic databases
PRIDE	Q96QV1.
Genome annotation databases
Ensembl	ENSG00000164161. Homo sapiens. [Contig view]
GeneID	64399.
KEGG	hsa:64399.
Organism-specific databases
GeneCards	GC04P145786.
HGNC	HGNC:14866. HHIP.
HPA	HPA012616.
MIM	606178. gene. 612226. phenotype.
PharmGKB	PA29276.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q96QV1.
HOVERGEN	Q96QV1.
OMA	Q96QV1. RNGNFLT.
Enzyme and pathway databases
Pathway_Interaction_DB	hedgehog_2pathway. Signaling events mediated by the Hedgehog family.
Gene expression databases
ArrayExpress	Q96QV1.
Bgee	Q96QV1.
CleanEx	HS_HHIP.
GermOnline	ENSG00000164161. Homo sapiens.
Family and domain databases
InterPro	IPR011042. 6-blade_b-propeller_TolB-like. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000742. EGF_3. IPR013111. EGF_extracell. IPR018143. Folate_rcpt_cons-reg. [Graphical view]
Gene3D	G3DSA:2.120.10.30. 6-blade_b-propeller_TolB-like. 1 hit.
Pfam	PF07974. EGF_2. 1 hit. PF03024. Folate_rec. 1 hit. [Graphical view]
SMART	SM00181. EGF. 2 hits. [Graphical view]
PROSITE	PS00022. EGF_1. 2 hits. PS01186. EGF_2. 2 hits. PS50026. EGF_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	66342.
SOURCE	Search...

Entry information

Entry name

HHIP_HUMAN

Accession

Primary (citable) accession number: Q96QV1
Secondary accession number(s): Q6PK09 , Q8NCI7, Q9BXK3, Q9H1J4, Q9H7E7

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 12, 2005
Last sequence update:	November 28, 2006
Last modified:	June 16, 2009
This is version 58 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)