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Protein

Hedgehog-interacting protein

Gene

HHIP

Organism
Homo sapiens (Human)
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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi383Zinc; shared with SHH1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164161-MONOMER.
ReactomeiR-HSA-5632681. Ligand-receptor interactions.
SignaLinkiQ96QV1.
SIGNORiQ96QV1.

Names & Taxonomyi

Protein namesi
Recommended name:
Hedgehog-interacting protein
Short name:
HHIP
Short name:
HIP
Gene namesi
Name:HHIP
Synonyms:HIP
ORF Names:UNQ5825/PRO19644
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:14866. HHIP.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: Ensembl
  • ciliary membrane Source: Reactome
  • cytoplasm Source: UniProtKB-SubCell
  • extracellular region Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi380E → A: Abolishes SHH binding. 1 Publication1
Mutagenesisi382M → A: Abolishes SHH binding. 1 Publication1
Mutagenesisi383D → A or R: Abolishes SHH binding. 2 Publications1
Mutagenesisi387D → A: Abolishes SHH binding. 1 Publication1

Organism-specific databases

DisGeNETi64399.
MIMi612224. phenotype.
OpenTargetsiENSG00000164161.
PharmGKBiPA29276.

Polymorphism and mutation databases

BioMutaiHHIP.
DMDMi118572655.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
ChainiPRO_000000762318 – 700Hedgehog-interacting proteinAdd BLAST683

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi99N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi216 ↔ 536
Disulfide bondi218 ↔ 543
Disulfide bondi402 ↔ 624
Glycosylationi416N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi435 ↔ 452
Glycosylationi447N-linked (GlcNAc...)1 Publication1
Glycosylationi459N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi500 ↔ 594
Disulfide bondi608 ↔ 617
Disulfide bondi612 ↔ 623
Disulfide bondi625 ↔ 634
Disulfide bondi639 ↔ 649
Disulfide bondi643 ↔ 655
Disulfide bondi657 ↔ 666

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ96QV1.
PaxDbiQ96QV1.
PeptideAtlasiQ96QV1.
PRIDEiQ96QV1.

PTM databases

iPTMnetiQ96QV1.
PhosphoSitePlusiQ96QV1.

Expressioni

Tissue specificityi

Widely expressed in fetal and adult tissues. Highest expression in adult heart, liver and pancreas, and in fetal kidney.2 Publications

Gene expression databases

BgeeiENSG00000164161.
CleanExiHS_HHIP.
GenevisibleiQ96QV1. HS.

Organism-specific databases

HPAiHPA012616.

Interactioni

Subunit structurei

Interacts with all three hedgehog family members, SHH, IHH and DHH.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
SHHQ1546510EBI-6598521,EBI-11666886

GO - Molecular functioni

  • hedgehog family protein binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi122156. 1 interactor.
DIPiDIP-48536N.
IntActiQ96QV1. 5 interactors.
STRINGi9606.ENSP00000296575.

Structurei

Secondary structure

1700
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi217 – 233Combined sources17
Beta strandi236 – 239Combined sources4
Beta strandi242 – 246Combined sources5
Turni247 – 249Combined sources3
Beta strandi250 – 254Combined sources5
Beta strandi256 – 258Combined sources3
Beta strandi265 – 267Combined sources3
Turni269 – 271Combined sources3
Beta strandi277 – 279Combined sources3
Beta strandi283 – 289Combined sources7
Helixi293 – 296Combined sources4
Beta strandi298 – 305Combined sources8
Beta strandi312 – 315Combined sources4
Beta strandi317 – 326Combined sources10
Helixi336 – 338Combined sources3
Beta strandi340 – 352Combined sources13
Beta strandi354 – 359Combined sources6
Helixi361 – 363Combined sources3
Beta strandi365 – 369Combined sources5
Helixi376 – 381Combined sources6
Beta strandi391 – 396Combined sources6
Beta strandi402 – 405Combined sources4
Turni413 – 416Combined sources4
Beta strandi418 – 420Combined sources3
Beta strandi424 – 427Combined sources4
Beta strandi430 – 432Combined sources3
Beta strandi434 – 440Combined sources7
Beta strandi442 – 445Combined sources4
Beta strandi447 – 453Combined sources7
Beta strandi457 – 459Combined sources3
Beta strandi463 – 468Combined sources6
Beta strandi481 – 483Combined sources3
Beta strandi491 – 496Combined sources6
Turni503 – 507Combined sources5
Beta strandi509 – 513Combined sources5
Beta strandi514 – 516Combined sources3
Beta strandi518 – 522Combined sources5
Beta strandi525 – 528Combined sources4
Beta strandi531 – 535Combined sources5
Beta strandi537 – 539Combined sources3
Beta strandi543 – 545Combined sources3
Beta strandi549 – 556Combined sources8
Beta strandi558 – 560Combined sources3
Beta strandi562 – 569Combined sources8
Helixi571 – 573Combined sources3
Beta strandi575 – 583Combined sources9
Beta strandi587 – 590Combined sources4
Helixi592 – 594Combined sources3
Helixi607 – 611Combined sources5
Beta strandi614 – 617Combined sources4
Beta strandi623 – 625Combined sources3
Beta strandi629 – 631Combined sources3
Beta strandi644 – 646Combined sources3
Beta strandi648 – 651Combined sources4
Beta strandi654 – 656Combined sources3
Beta strandi661 – 663Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WFTX-ray2.80A/B214-671[»]
2WFXX-ray3.20B214-670[»]
2WG3X-ray2.60C/D214-670[»]
2WG4X-ray3.15B214-670[»]
3HO3X-ray2.90A193-667[»]
3HO4X-ray3.10A/B193-667[»]
3HO5X-ray3.01A/B193-667[»]
ProteinModelPortaliQ96QV1.
SMRiQ96QV1.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96QV1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini607 – 634EGF-like 1PROSITE-ProRule annotationAdd BLAST28
Domaini635 – 667EGF-like 2PROSITE-ProRule annotationAdd BLAST33

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni376 – 388Interaction with SHH zinc binding siteAdd BLAST13

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi35 – 54Arg-richAdd BLAST20

Domaini

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

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

eggNOGiENOG410IEIH. Eukaryota.
ENOG410ZT1I. LUCA.
GeneTreeiENSGT00530000063250.
HOGENOMiHOG000008644.
HOVERGENiHBG051901.
InParanoidiQ96QV1.
KOiK06231.
OMAiEPFLDIH.
OrthoDBiEOG091G01D0.
PhylomeDBiQ96QV1.
TreeFamiTF329059.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
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]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96QV1-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MLKMLSFKLL LLAVALGFFE GDAKFGERNE GSGARRRRCL NGNPPKRLKR
60 70 80 90 100
RDRRMMSQLE LLSGGEMLCG GFYPRLSCCL RSDSPGLGRL ENKIFSVTNN
110 120 130 140 150
TECGKLLEEI KCALCSPHSQ SLFHSPEREV LERDLVLPLL CKDYCKEFFY
160 170 180 190 200
TCRGHIPGFL QTTADEFCFY YARKDGGLCF PDFPRKQVRG PASNYLDQME
210 220 230 240 250
EYDKVEEISR KHKHNCFCIQ EVVSGLRQPV GALHSGDGSQ RLFILEKEGY
260 270 280 290 300
VKILTPEGEI FKEPYLDIHK LVQSGIKGGD ERGLLSLAFH PNYKKNGKLY
310 320 330 340 350
VSYTTNQERW AIGPHDHILR VVEYTVSRKN PHQVDLRTAR 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 GKDYESEPSL LEFKPFSNGP LVGGFVYRGC
510 520 530 540 550
QSERLYGSYV FGDRNGNFLT LQQSPVTKQW QEKPLCLGTS GSCRGYFSGH
560 570 580 590 600
ILGFGEDELG EVYILSSSKS MTQTHNGKLY KIVDPKRPLM PEECRATVQP
610 620 630 640 650
AQTLTSECSR LCRNGYCTPT GKCCCSPGWE GDFCRTAKCE PACRHGGVCV
660 670 680 690 700
RPNKCLCKKG YLGPQCEQVD RNIRRVTRAG ILDQIIDMTS YLLDLTSYIV
Length:700
Mass (Da):78,851
Last modified:November 28, 2006 - v3
Checksum:iCC1CB3435E29303A
GO
Isoform 2 (identifier: Q96QV1-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:320
Mass (Da):36,373
Checksum:i3AF86509A46A7676
GO

Sequence cautioni

The sequence BAB14945 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti126P → L in BAC11154 (PubMed:14702039).Curated1
Sequence conflicti135L → I in AAG34731 (Ref. 1) Curated1
Sequence conflicti173R → G in BAC11154 (PubMed:14702039).Curated1

Polymorphismi

Genetic variations in HHIP define the stature quantitative trait locus 12 (STQTL12) [MIMi:612224]. 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.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021518341V → I.2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013192278 – 320GGDER…DHILR → VGFLNFIYFCAGYVNFILVL PSSLKVFLCNKRKNLAGENK GAT in isoform 2. 2 PublicationsAdd BLAST43
Alternative sequenceiVSP_013193321 – 700Missing in isoform 2. 2 PublicationsAdd BLAST380

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AC098588 Genomic DNA. No translation available.
BC009298 mRNA. Translation: AAH09298.1.
BC025311 mRNA. Translation: AAH25311.1.
CCDSiCCDS3762.1. [Q96QV1-1]
RefSeqiNP_071920.1. NM_022475.2. [Q96QV1-1]
UniGeneiHs.507991.

Genome annotation databases

EnsembliENST00000296575; ENSP00000296575; ENSG00000164161. [Q96QV1-1]
ENST00000434550; ENSP00000408587; ENSG00000164161. [Q96QV1-2]
GeneIDi64399.
KEGGihsa:64399.
UCSCiuc003ijr.3. human. [Q96QV1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
AC098588 Genomic DNA. No translation available.
BC009298 mRNA. Translation: AAH09298.1.
BC025311 mRNA. Translation: AAH25311.1.
CCDSiCCDS3762.1. [Q96QV1-1]
RefSeqiNP_071920.1. NM_022475.2. [Q96QV1-1]
UniGeneiHs.507991.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WFTX-ray2.80A/B214-671[»]
2WFXX-ray3.20B214-670[»]
2WG3X-ray2.60C/D214-670[»]
2WG4X-ray3.15B214-670[»]
3HO3X-ray2.90A193-667[»]
3HO4X-ray3.10A/B193-667[»]
3HO5X-ray3.01A/B193-667[»]
ProteinModelPortaliQ96QV1.
SMRiQ96QV1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122156. 1 interactor.
DIPiDIP-48536N.
IntActiQ96QV1. 5 interactors.
STRINGi9606.ENSP00000296575.

PTM databases

iPTMnetiQ96QV1.
PhosphoSitePlusiQ96QV1.

Polymorphism and mutation databases

BioMutaiHHIP.
DMDMi118572655.

Proteomic databases

EPDiQ96QV1.
PaxDbiQ96QV1.
PeptideAtlasiQ96QV1.
PRIDEiQ96QV1.

Protocols and materials databases

DNASUi64399.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296575; ENSP00000296575; ENSG00000164161. [Q96QV1-1]
ENST00000434550; ENSP00000408587; ENSG00000164161. [Q96QV1-2]
GeneIDi64399.
KEGGihsa:64399.
UCSCiuc003ijr.3. human. [Q96QV1-1]

Organism-specific databases

CTDi64399.
DisGeNETi64399.
GeneCardsiHHIP.
HGNCiHGNC:14866. HHIP.
HPAiHPA012616.
MIMi606178. gene.
612224. phenotype.
neXtProtiNX_Q96QV1.
OpenTargetsiENSG00000164161.
PharmGKBiPA29276.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEIH. Eukaryota.
ENOG410ZT1I. LUCA.
GeneTreeiENSGT00530000063250.
HOGENOMiHOG000008644.
HOVERGENiHBG051901.
InParanoidiQ96QV1.
KOiK06231.
OMAiEPFLDIH.
OrthoDBiEOG091G01D0.
PhylomeDBiQ96QV1.
TreeFamiTF329059.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000164161-MONOMER.
ReactomeiR-HSA-5632681. Ligand-receptor interactions.
SignaLinkiQ96QV1.
SIGNORiQ96QV1.

Miscellaneous databases

ChiTaRSiHHIP. human.
EvolutionaryTraceiQ96QV1.
GeneWikiiHHIP.
GenomeRNAii64399.
PROiQ96QV1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164161.
CleanExiHS_HHIP.
GenevisibleiQ96QV1. HS.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
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...

Entry informationi

Entry nameiHHIP_HUMAN
AccessioniPrimary (citable) accession number: Q96QV1
Secondary accession number(s): Q6PK09
, Q8NCI7, Q9BXK3, Q9H1J4, Q9H7E7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: November 28, 2006
Last modified: November 2, 2016
This is version 129 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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 one 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.