UniProtKB - O00291 (HIP1_HUMAN)
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Protein
Huntingtin-interacting protein 1
Gene
HIP1
Organism
Homo sapiens (Human)
Status
Functioni
Plays a role in clathrin-mediated endocytosis and trafficking (PubMed:11532990, PubMed:11577110, PubMed:11889126). Involved in regulating AMPA receptor trafficking in the central nervous system in an NMDA-dependent manner (By similarity). Regulates presynaptic nerve terminal activity (By similarity). Enhances androgen receptor (AR)-mediated transcription (PubMed:16027218). May act as a proapoptotic protein that induces cell death by acting through the intrinsic apoptosis pathway (PubMed:11007801). Binds 3-phosphoinositides (via ENTH domain) (PubMed:14732715). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis (PubMed:14732715). May play a functional role in the cell filament networks (PubMed:18790740). May be required for differentiation, proliferation, and/or survival of somatic and germline progenitors (PubMed:11007801, PubMed:12163454).By similarity9 Publications
Miscellaneous
The affinity of the huntingtin protein-HIP1 interaction is inversely correlated to the length of the polyglutamine tract added to the huntingtin protein in Huntington disease.
GO - Molecular functioni
- actin filament binding Source: ParkinsonsUK-UCL
- AP-2 adaptor complex binding Source: ParkinsonsUK-UCL
- clathrin adaptor activity Source: ParkinsonsUK-UCL
- clathrin binding Source: ParkinsonsUK-UCL
- clathrin light chain binding Source: ParkinsonsUK-UCL
- epidermal growth factor receptor binding Source: ParkinsonsUK-UCL
- glutamate receptor binding Source: ParkinsonsUK-UCL
- phosphatidylinositol-3,4-bisphosphate binding Source: ParkinsonsUK-UCL
- phosphatidylinositol-3,5-bisphosphate binding Source: ParkinsonsUK-UCL
- phosphatidylinositol-3-phosphate binding Source: ParkinsonsUK-UCL
- phosphatidylinositol binding Source: UniProtKB
- protein heterodimerization activity Source: ParkinsonsUK-UCL
- protein homodimerization activity Source: ParkinsonsUK-UCL
- structural constituent of cytoskeleton Source: ProtInc
GO - Biological processi
- activation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
- apoptotic process Source: MGI
- apoptotic signaling pathway Source: UniProtKB
- cell differentiation Source: UniProtKB-KW
- clathrin coat assembly Source: UniProtKB
- clathrin-dependent endocytosis Source: InterPro
- membrane organization Source: Reactome
- neurotransmitter receptor transport Source: ParkinsonsUK-UCL
- positive regulation of epidermal growth factor receptor signaling pathway Source: ParkinsonsUK-UCL
- positive regulation of platelet-derived growth factor receptor-beta signaling pathway Source: ParkinsonsUK-UCL
- positive regulation of protein kinase B signaling Source: ParkinsonsUK-UCL
- positive regulation of receptor-mediated endocytosis Source: UniProtKB
- protein stabilization Source: ParkinsonsUK-UCL
- regulation of apoptotic process Source: MGI
- regulation of endocytosis Source: ParkinsonsUK-UCL
- regulation of transcription, DNA-templated Source: UniProtKB-KW
- transcription, DNA-templated Source: UniProtKB-KW
Keywordsi
Molecular function | Actin-binding, Activator |
Biological process | Apoptosis, Differentiation, Endocytosis, Transcription, Transcription regulation |
Enzyme and pathway databases
Reactomei | R-HSA-8856828. Clathrin-mediated endocytosis. |
SIGNORi | O00291. |
Names & Taxonomyi
Protein namesi | Recommended name: Huntingtin-interacting protein 1Short name: HIP-1 Alternative name(s): Huntingtin-interacting protein I Short name: HIP-I |
Gene namesi | Name:HIP1 |
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
EuPathDBi | HostDB:ENSG00000127946.16. |
HGNCi | HGNC:4913. HIP1. |
MIMi | 601767. gene. |
neXtProti | NX_O00291. |
Subcellular locationi
Keywords - Cellular componenti
Cytoplasm, Cytoplasmic vesicle, Membrane, NucleusPathology & Biotechi
Involvement in diseasei
A chromosomal aberration involving HIP1 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;7)(q33;q11.2) with PDGFRB (PubMed:9616134). The chimeric HIP1-PDGFRB transcript results from an in-frame fusion of the two genes (PubMed:9616134). The reciprocal PDGFRB-HIP1 transcript is not expressed (PubMed:9616134).1 Publication
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 56 | K → E: Abolishes 3-phosphoinositide-binding; when associated with E-58. 1 Publication | 1 | |
Mutagenesisi | 58 | K → E: Abolishes 3-phosphoinositide-binding; when associated with E-56. 1 Publication | 1 | |
Mutagenesisi | 432 | F → G: Abolishes HIP1-induced cell death. 1 Publication | 1 | |
Mutagenesisi | 1005 | R → E: Reduces AR-induced nuclear translocation. 1 Publication | 1 |
Keywords - Diseasei
NeurodegenerationOrganism-specific databases
DisGeNETi | 3092. |
MalaCardsi | HIP1. |
OpenTargetsi | ENSG00000127946. |
PharmGKBi | PA29289. |
Polymorphism and mutation databases
BioMutai | HIP1. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000083986 | 1 – 1037 | Huntingtin-interacting protein 1Add BLAST | 1037 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 338 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | O00291. |
PaxDbi | O00291. |
PeptideAtlasi | O00291. |
PRIDEi | O00291. |
PTM databases
iPTMneti | O00291. |
PhosphoSitePlusi | O00291. |
SwissPalmi | O00291. |
Expressioni
Tissue specificityi
Ubiquitously expressed with the highest level in brain. Expression is up-regulated in prostate and colon cancer.3 Publications
Gene expression databases
Bgeei | ENSG00000127946. |
CleanExi | HS_HIP1. |
ExpressionAtlasi | O00291. baseline and differential. |
Genevisiblei | O00291. HS. |
Organism-specific databases
HPAi | CAB015334. CAB016402. HPA013606. HPA017964. |
Interactioni
Subunit structurei
Homodimer. Binds actin. Binds HTT (via N-terminus). This interaction is restricted to the brain. Binds to IFT57. In normal conditions, it poorly interacts with IFT57, HIP1 being strongly associated with HTT. However, in mutant HTT proteins with a long poly-Gln region, interaction between HTT and HIP1 is inhibited, promoting the interaction between HIP1 and IFT57. Interacts with CLTB (via N-terminus). Interacts (via coiled coil domain) with AR. Interacts with AP2A1, AP2A2, CLTC and HIP1R. Interacts with GRIA1, GRIN2A AND GRIN2B.8 Publications
Binary interactionsi
GO - Molecular functioni
- actin filament binding Source: ParkinsonsUK-UCL
- AP-2 adaptor complex binding Source: ParkinsonsUK-UCL
- clathrin adaptor activity Source: ParkinsonsUK-UCL
- clathrin binding Source: ParkinsonsUK-UCL
- clathrin light chain binding Source: ParkinsonsUK-UCL
- epidermal growth factor receptor binding Source: ParkinsonsUK-UCL
- glutamate receptor binding Source: ParkinsonsUK-UCL
- protein heterodimerization activity Source: ParkinsonsUK-UCL
- protein homodimerization activity Source: ParkinsonsUK-UCL
Protein-protein interaction databases
BioGridi | 109339. 29 interactors. |
DIPi | DIP-17041N. |
ELMi | O00291. |
IntActi | O00291. 39 interactors. |
MINTi | O00291. |
STRINGi | 9606.ENSP00000336747. |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Helixi | 373 – 441 | Combined sources | 69 | |
Turni | 459 – 461 | Combined sources | 3 | |
Helixi | 462 – 465 | Combined sources | 4 | |
Helixi | 482 – 580 | Combined sources | 99 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2NO2 | X-ray | 2.80 | A | 482-586 | [»] | |
2QA7 | X-ray | 2.80 | A/B/C/D | 370-481 | [»] | |
3I00 | X-ray | 2.30 | A/B | 361-480 | [»] | |
ProteinModelPortali | O00291. | |||||
SMRi | O00291. | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O00291. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 32 – 160 | ENTHPROSITE-ProRule annotationAdd BLAST | 129 | |
Domaini | 771 – 1012 | I/LWEQPROSITE-ProRule annotationAdd BLAST | 242 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 410 – 491 | pDEDAdd BLAST | 82 | |
Regioni | 867 – 924 | Important for actin bindingBy similarityAdd BLAST | 58 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 368 – 644 | Sequence analysisAdd BLAST | 277 |
Domaini
The pseudo DED region (pDED) mediates the interaction with IFT57.1 Publication
Binds F-actin via the talin-like I/LWEQ domain.1 Publication
Sequence similaritiesi
Belongs to the SLA2 family.Curated
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG0980. Eukaryota. ENOG410XRXQ. LUCA. |
GeneTreei | ENSGT00550000074542. |
HOGENOMi | HOG000020612. |
HOVERGENi | HBG005968. |
InParanoidi | O00291. |
KOi | K04559. |
OMAi | NNRWTEG. |
OrthoDBi | EOG091G07Y5. |
PhylomeDBi | O00291. |
TreeFami | TF316860. |
Family and domain databases
Gene3Di | 1.25.40.90. 1 hit. |
InterProi | View protein in InterPro IPR011417. ANTH_dom. IPR013809. ENTH. IPR008942. ENTH_VHS. IPR030554. HIP1. IPR032422. HIP1_clath-bd. IPR035964. I/LWEQ_dom_sf. IPR002558. ILWEQ_dom. IPR030224. Sla2_fam. |
PANTHERi | PTHR10407. PTHR10407. 1 hit. PTHR10407:SF14. PTHR10407:SF14. 1 hit. |
Pfami | View protein in Pfam PF07651. ANTH. 1 hit. PF16515. HIP1_clath_bdg. 1 hit. PF01608. I_LWEQ. 1 hit. |
ProDomi | View protein in ProDom or Entries sharing at least one domain PD011820. ILWEQ. 1 hit. |
SMARTi | View protein in SMART SM00273. ENTH. 1 hit. SM00307. ILWEQ. 1 hit. |
SUPFAMi | SSF109885. SSF109885. 1 hit. SSF48464. SSF48464. 1 hit. |
PROSITEi | View protein in PROSITE PS50942. ENTH. 1 hit. PS50945. I_LWEQ. 1 hit. |
s (4)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basket
Isoform HIP1-1 (identifier: O00291-1) [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.
10 20 30 40 50
MDRMASSMKQ VPNPLPKVLS RRGVGAGLEA AERESFERTQ TVSINKAINT
60 70 80 90 100
QEVAVKEKHA RTCILGTHHE KGAQTFWSVV NRLPLSSNAV LCWKFCHVFH
110 120 130 140 150
KLLRDGHPNV LKDSLRYRNE LSDMSRMWGH LSEGYGQLCS IYLKLLRTKM
160 170 180 190 200
EYHTKNPRFP GNLQMSDRQL DEAGESDVNN FFQLTVEMFD YLECELNLFQ
210 220 230 240 250
TVFNSLDMSR SVSVTAAGQC RLAPLIQVIL DCSHLYDYTV KLLFKLHSCL
260 270 280 290 300
PADTLQGHRD RFMEQFTKLK DLFYRSSNLQ YFKRLIQIPQ LPENPPNFLR
310 320 330 340 350
ASALSEHISP VVVIPAEASS PDSEPVLEKD DLMDMDASQQ NLFDNKFDDI
360 370 380 390 400
FGSSFSSDPF NFNSQNGVNK DEKDHLIERL YREISGLKAQ LENMKTESQR
410 420 430 440 450
VVLQLKGHVS ELEADLAEQQ HLRQQAADDC EFLRAELDEL RRQREDTEKA
460 470 480 490 500
QRSLSEIERK AQANEQRYSK LKEKYSELVQ NHADLLRKNA EVTKQVSMAR
510 520 530 540 550
QAQVDLEREK KELEDSLERI SDQGQRKTQE QLEVLESLKQ ELATSQRELQ
560 570 580 590 600
VLQGSLETSA QSEANWAAEF AELEKERDSL VSGAAHREEE LSALRKELQD
610 620 630 640 650
TQLKLASTEE SMCQLAKDQR KMLLVGSRKA AEQVIQDALN QLEEPPLISC
660 670 680 690 700
AGSADHLLST VTSISSCIEQ LEKSWSQYLA CPEDISGLLH SITLLAHLTS
710 720 730 740 750
DAIAHGATTC LRAPPEPADS LTEACKQYGR ETLAYLASLE EEGSLENADS
760 770 780 790 800
TAMRNCLSKI KAIGEELLPR GLDIKQEELG DLVDKEMAAT SAAIETATAR
810 820 830 840 850
IEEMLSKSRA GDTGVKLEVN ERILGCCTSL MQAIQVLIVA SKDLQREIVE
860 870 880 890 900
SGRGTASPKE FYAKNSRWTE GLISASKAVG WGATVMVDAA DLVVQGRGKF
910 920 930 940 950
EELMVCSHEI AASTAQLVAA SKVKADKDSP NLAQLQQASR GVNQATAGVV
960 970 980 990 1000
ASTISGKSQI EETDNMDFSS MTLTQIKRQE MDSQVRVLEL ENELQKERQK
1010 1020 1030
LGELRKKHYE LAGVAEGWEE GTEASPPTLQ EVVTEKE
Isoform HIP1-2 (identifier: O00291-2)
Sequence is not available
Length:–
Mass (Da):–
Sequence cautioni
The sequence AAC51257 differs from that shown. Reason: Erroneous initiation.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 89 | A → P in AAC33564 (PubMed:11788820).Curated | 1 | |
Sequence conflicti | 245 – 251 | KLHSCLP → EFAAAST in CAA70574 (PubMed:9147654).Curated | 7 | |
Sequence conflicti | 357 | S → R in BAG65499 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 639 – 644 | LNQLEE → STRPRI in CAA70574 (PubMed:9147654).Curated | 6 | |
Sequence conflicti | 688 | L → F in AAL87037 (PubMed:11788820).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_051032 | 263 | M → K. Corresponds to variant dbSNP:rs17149023Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_057400 | 1 – 40 | MDRMA…FERTQ → MMFPNPEPPPE in isoform 4. 1 PublicationAdd BLAST | 40 | |
Alternative sequenceiVSP_044736 | 803 – 853 | Missing in isoform 3. 1 PublicationAdd BLAST | 51 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | KF437291 mRNA. Translation: AHA56631.1. AK304738 mRNA. Translation: BAG65499.1. AC004491 Genomic DNA. No translation available. AC018720 Genomic DNA. No translation available. AC211429 Genomic DNA. No translation available. KF495977 Genomic DNA. No translation available. BC110545 mRNA. Translation: AAI10546.1. AF365404 mRNA. Translation: AAL87037.1. AH006397 Genomic DNA. Translation: AAC33564.1. U79734 mRNA. Translation: AAC51257.1. Different initiation. Y09420 mRNA. Translation: CAA70574.1. |
CCDSi | CCDS34669.1. [O00291-1] CCDS59060.1. [O00291-3] |
RefSeqi | NP_001230127.1. NM_001243198.2. [O00291-3] NP_005329.3. NM_005338.6. [O00291-1] XP_005250361.1. XM_005250304.2. [O00291-4] XP_011514418.1. XM_011516116.2. [O00291-1] |
UniGenei | Hs.329266. Hs.619089. Hs.674397. |
Genome annotation databases
Ensembli | ENST00000336926; ENSP00000336747; ENSG00000127946. [O00291-1] ENST00000434438; ENSP00000410300; ENSG00000127946. [O00291-3] ENST00000616821; ENSP00000484528; ENSG00000127946. [O00291-4] |
GeneIDi | 3092. |
KEGGi | hsa:3092. |
UCSCi | uc003uds.4. human. [O00291-1] uc064emn.1. human. |
Keywords - Coding sequence diversityi
Alternative splicing, Chromosomal rearrangement, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | HIP1_HUMAN | |
Accessioni | O00291Primary (citable) accession number: O00291 Secondary accession number(s): B4E3I7 V5LU97 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 27, 2001 |
Last sequence update: | September 23, 2008 | |
Last modified: | March 28, 2018 | |
This is version 184 of the entry and version 5 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. |