UniProtKB - Q96QV1 (HHIP_HUMAN)
Protein
Hedgehog-interacting protein
Gene
HHIP
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 383 | Zinc; shared with SHH | 1 |
GO - Molecular functioni
- catalytic activity Source: InterPro
- hedgehog family protein binding Source: BHF-UCL
- zinc ion binding Source: UniProtKB
GO - Biological processi
- dorsal/ventral pattern formation Source: Ensembl
- epithelial tube branching involved in lung morphogenesis Source: Ensembl
- negative regulation of apoptotic process Source: Ensembl
- negative regulation of signal transduction Source: UniProtKB
- negative regulation of smoothened signaling pathway Source: BHF-UCL
- neuroblast proliferation Source: Ensembl
- regulation of fibroblast growth factor receptor signaling pathway Source: Ensembl
- signal transduction Source: Ensembl
- skeletal system morphogenesis Source: BHF-UCL
Keywordsi
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q96QV1 |
Reactomei | R-HSA-5632681, Ligand-receptor interactions |
SignaLinki | Q96QV1 |
SIGNORi | Q96QV1 |
Names & Taxonomyi
Protein namesi | Recommended name: Hedgehog-interacting proteinShort name: HHIP Short name: HIP |
Gene namesi | Name:HHIP Synonyms:HIP ORF Names:UNQ5825/PRO19644 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:14866, HHIP |
MIMi | 606178, gene |
neXtProti | NX_Q96QV1 |
VEuPathDBi | HostDB:ENSG00000164161.9 |
Subcellular locationi
Plasma membrane
- Cell membrane By similarity; Peripheral membrane protein By similarity
Extracellular region or secreted
- Secreted By similarity
Note: The last 22 C-terminal amino acids may participate in cell membrane attachment.
Other locations
- Cytoplasm Curated
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Nucleus
- nucleus Source: Ensembl
Plasma Membrane
- ciliary membrane Source: Reactome
- integral component of plasma membrane Source: BHF-UCL
Other locations
- cell surface Source: Ensembl
- cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell membrane, Cytoplasm, Membrane, SecretedPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 380 | E → A: Abolishes SHH binding. 1 Publication | 1 | |
Mutagenesisi | 382 | M → A: Abolishes SHH binding. 1 Publication | 1 | |
Mutagenesisi | 383 | D → A or R: Abolishes SHH binding. 2 Publications | 1 | |
Mutagenesisi | 387 | D → A: Abolishes SHH binding. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 64399 |
MIMi | 612224, phenotype |
OpenTargetsi | ENSG00000164161 |
PharmGKBi | PA29276 |
Miscellaneous databases
Pharosi | Q96QV1, Tbio |
Genetic variation databases
BioMutai | HHIP |
DMDMi | 118572655 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 17 | Sequence analysisAdd BLAST | 17 | |
ChainiPRO_0000007623 | 18 – 700 | Hedgehog-interacting proteinAdd BLAST | 683 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 99 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 216 ↔ 536 | |||
Disulfide bondi | 218 ↔ 543 | |||
Disulfide bondi | 402 ↔ 624 | |||
Glycosylationi | 416 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 435 ↔ 452 | |||
Glycosylationi | 447 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 459 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 500 ↔ 594 | |||
Disulfide bondi | 608 ↔ 617 | |||
Disulfide bondi | 612 ↔ 623 | |||
Disulfide bondi | 625 ↔ 634 | |||
Disulfide bondi | 639 ↔ 649 | |||
Disulfide bondi | 643 ↔ 655 | |||
Disulfide bondi | 657 ↔ 666 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | Q96QV1 |
MassIVEi | Q96QV1 |
PaxDbi | Q96QV1 |
PeptideAtlasi | Q96QV1 |
PRIDEi | Q96QV1 |
ProteomicsDBi | 77909 [Q96QV1-1] 77910 [Q96QV1-2] |
PTM databases
GlyGeni | Q96QV1, 4 sites |
iPTMneti | Q96QV1 |
PhosphoSitePlusi | Q96QV1 |
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
Bgeei | ENSG00000164161, Expressed in corpus callosum and 171 other tissues |
Genevisiblei | Q96QV1, HS |
Organism-specific databases
HPAi | ENSG00000164161, Tissue enhanced (brain, lung) |
Interactioni
Subunit structurei
Interacts with all three hedgehog family members, SHH, IHH and DHH.
3 PublicationsBinary interactionsi
Hide detailsQ96QV1
With | #Exp. | IntAct |
---|---|---|
SHH [Q15465] | 10 | EBI-6598521,EBI-11666886 |
Isoform 1 [Q96QV1-1]
With | #Exp. | IntAct |
---|---|---|
DHH [O43323] | 4 | EBI-15791478,EBI-11667804 |
Shh [Q62226] from Mus musculus. | 4 | EBI-15791478,EBI-15610166 |
GO - Molecular functioni
- hedgehog family protein binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 122156, 1 interactor |
DIPi | DIP-48536N |
IntActi | Q96QV1, 6 interactors |
STRINGi | 9606.ENSP00000296575 |
Miscellaneous databases
RNActi | Q96QV1, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q96QV1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q96QV1 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 607 – 634 | EGF-like 1PROSITE-ProRule annotationAdd BLAST | 28 | |
Domaini | 635 – 667 | EGF-like 2PROSITE-ProRule annotationAdd BLAST | 33 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 376 – 388 | Interaction with SHH zinc binding siteAdd BLAST | 13 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 35 – 54 | Arg-richAdd BLAST | 20 |
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, SignalPhylogenomic databases
eggNOGi | KOG4295, Eukaryota |
GeneTreei | ENSGT00940000158660 |
HOGENOMi | CLU_012344_0_0_1 |
InParanoidi | Q96QV1 |
OMAi | NCFCVQE |
OrthoDBi | 728630at2759 |
PhylomeDBi | Q96QV1 |
TreeFami | TF329059 |
Family and domain databases
Gene3Di | 2.120.10.30, 1 hit |
InterProi | View protein in InterPro IPR011042, 6-blade_b-propeller_TolB-like IPR000742, EGF-like_dom IPR018143, Folate_rcpt-like IPR012938, Glc/Sorbosone_DH IPR011041, Quinoprot_gluc/sorb_DH |
Pfami | View protein in Pfam PF03024, Folate_rec, 1 hit PF07995, GSDH, 1 hit |
SMARTi | View protein in SMART SM00181, EGF, 2 hits |
SUPFAMi | SSF50952, SSF50952, 1 hit |
PROSITEi | View protein in PROSITE PS00022, EGF_1, 2 hits PS01186, EGF_2, 2 hits PS50026, EGF_3, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform 1 (identifier: Q96QV1-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Sequence cautioni
The sequence BAB14945 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 126 | P → L in BAC11154 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 135 | L → I in AAG34731 (Ref. 1) Curated | 1 | |
Sequence conflicti | 173 | R → G in BAC11154 (PubMed:14702039).Curated | 1 |
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_021518 | 341 | V → I2 Publications | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_013192 | 278 – 320 | GGDER…DHILR → VGFLNFIYFCAGYVNFILVL PSSLKVFLCNKRKNLAGENK GAT in isoform 2. 2 PublicationsAdd BLAST | 43 | |
Alternative sequenceiVSP_013193 | 321 – 700 | Missing in isoform 2. 2 PublicationsAdd BLAST | 380 |
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 |
CCDSi | CCDS3762.1 [Q96QV1-1] |
RefSeqi | NP_071920.1, NM_022475.2 [Q96QV1-1] |
Genome annotation databases
Ensembli | ENST00000296575; ENSP00000296575; ENSG00000164161 [Q96QV1-1] ENST00000434550; ENSP00000408587; ENSG00000164161 [Q96QV1-2] |
GeneIDi | 64399 |
KEGGi | hsa:64399 |
UCSCi | uc003ijr.3, human [Q96QV1-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS3762.1 [Q96QV1-1] |
RefSeqi | NP_071920.1, NM_022475.2 [Q96QV1-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2WFT | X-ray | 2.80 | A/B | 214-671 | [»] | |
2WFX | X-ray | 3.20 | B | 214-670 | [»] | |
2WG3 | X-ray | 2.60 | C/D | 214-670 | [»] | |
2WG4 | X-ray | 3.15 | B | 214-670 | [»] | |
3HO3 | X-ray | 2.90 | A | 193-667 | [»] | |
3HO4 | X-ray | 3.10 | A/B | 193-667 | [»] | |
3HO5 | X-ray | 3.01 | A/B | 193-667 | [»] | |
SMRi | Q96QV1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 122156, 1 interactor |
DIPi | DIP-48536N |
IntActi | Q96QV1, 6 interactors |
STRINGi | 9606.ENSP00000296575 |
PTM databases
GlyGeni | Q96QV1, 4 sites |
iPTMneti | Q96QV1 |
PhosphoSitePlusi | Q96QV1 |
Genetic variation databases
BioMutai | HHIP |
DMDMi | 118572655 |
Proteomic databases
EPDi | Q96QV1 |
MassIVEi | Q96QV1 |
PaxDbi | Q96QV1 |
PeptideAtlasi | Q96QV1 |
PRIDEi | Q96QV1 |
ProteomicsDBi | 77909 [Q96QV1-1] 77910 [Q96QV1-2] |
Protocols and materials databases
Antibodypediai | 2783, 230 antibodies |
DNASUi | 64399 |
Genome annotation databases
Ensembli | ENST00000296575; ENSP00000296575; ENSG00000164161 [Q96QV1-1] ENST00000434550; ENSP00000408587; ENSG00000164161 [Q96QV1-2] |
GeneIDi | 64399 |
KEGGi | hsa:64399 |
UCSCi | uc003ijr.3, human [Q96QV1-1] |
Organism-specific databases
CTDi | 64399 |
DisGeNETi | 64399 |
GeneCardsi | HHIP |
HGNCi | HGNC:14866, HHIP |
HPAi | ENSG00000164161, Tissue enhanced (brain, lung) |
MIMi | 606178, gene 612224, phenotype |
neXtProti | NX_Q96QV1 |
OpenTargetsi | ENSG00000164161 |
PharmGKBi | PA29276 |
VEuPathDBi | HostDB:ENSG00000164161.9 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4295, Eukaryota |
GeneTreei | ENSGT00940000158660 |
HOGENOMi | CLU_012344_0_0_1 |
InParanoidi | Q96QV1 |
OMAi | NCFCVQE |
OrthoDBi | 728630at2759 |
PhylomeDBi | Q96QV1 |
TreeFami | TF329059 |
Enzyme and pathway databases
PathwayCommonsi | Q96QV1 |
Reactomei | R-HSA-5632681, Ligand-receptor interactions |
SignaLinki | Q96QV1 |
SIGNORi | Q96QV1 |
Miscellaneous databases
BioGRID-ORCSi | 64399, 5 hits in 870 CRISPR screens |
ChiTaRSi | HHIP, human |
EvolutionaryTracei | Q96QV1 |
GeneWikii | HHIP |
GenomeRNAii | 64399 |
Pharosi | Q96QV1, Tbio |
PROi | PR:Q96QV1 |
RNActi | Q96QV1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000164161, Expressed in corpus callosum and 171 other tissues |
Genevisiblei | Q96QV1, HS |
Family and domain databases
Gene3Di | 2.120.10.30, 1 hit |
InterProi | View protein in InterPro IPR011042, 6-blade_b-propeller_TolB-like IPR000742, EGF-like_dom IPR018143, Folate_rcpt-like IPR012938, Glc/Sorbosone_DH IPR011041, Quinoprot_gluc/sorb_DH |
Pfami | View protein in Pfam PF03024, Folate_rec, 1 hit PF07995, GSDH, 1 hit |
SMARTi | View protein in SMART SM00181, EGF, 2 hits |
SUPFAMi | SSF50952, SSF50952, 1 hit |
PROSITEi | View protein in PROSITE PS00022, EGF_1, 2 hits PS01186, EGF_2, 2 hits PS50026, EGF_3, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HHIP_HUMAN | |
Accessioni | Q96QV1Primary (citable) accession number: Q96QV1 Secondary accession number(s): Q6PK09 Q9H7E7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 12, 2005 |
Last sequence update: | November 28, 2006 | |
Last modified: | February 10, 2021 | |
This is version 156 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants