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Protein

Hedgehog-interacting protein

Gene

HHIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • catalytic activity Source: InterPro
  • hedgehog family protein binding Source: BHF-UCL
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Keywordsi

LigandMetal-binding, Zinc

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000164161.9
HGNCiHGNC:14866 HHIP
MIMi606178 gene
neXtProtiNX_Q96QV1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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...) asparagineSequence analysis1
Disulfide bondi216 ↔ 536
Disulfide bondi218 ↔ 543
Disulfide bondi402 ↔ 624
Glycosylationi416N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi435 ↔ 452
Glycosylationi447N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi459N-linked (GlcNAc...) asparagineSequence 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
ProteomicsDBi77909
77910 [Q96QV1-2]

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 Expressed in 149 organ(s), highest expression level in corpus callosum
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122156, 1 interactor
DIPiDIP-48536N
IntActiQ96QV1, 6 interactors
STRINGi9606.ENSP00000296575

Structurei

Secondary structure

1700
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

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

Family and domain databases

Gene3Di2.120.10.30, 1 hit
InterProiView protein in InterPro
IPR011042 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
PfamiView protein in Pfam
PF03024 Folate_rec, 1 hit
PF07995 GSDH, 1 hit
SMARTiView protein in SMART
SM00181 EGF, 2 hits
SUPFAMiSSF50952 SSF50952, 1 hit
PROSITEiView protein in PROSITE
PS00022 EGF_1, 2 hits
PS01186 EGF_2, 2 hits
PS50026 EGF_3, 1 hit

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 → I2 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

Similar proteinsi

Entry informationi

Entry nameiHHIP_HUMAN
AccessioniPrimary (citable) accession number: Q96QV1
Secondary accession number(s): Q6PK09
, Q8NCI7, Q9BXK3, Q9H1J4, Q9H7E7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: November 28, 2006
Last modified: September 12, 2018
This is version 139 of the entry and version 3 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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