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Protein

Huntingtin-interacting protein 1

Gene

HIP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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 functionActin-binding, Activator
Biological processApoptosis, Differentiation, Endocytosis, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-8856828 Clathrin-mediated endocytosis
SIGNORiO00291

Protein family/group databases

MoonDBiO00291 Curated

Names & Taxonomyi

Protein namesi
Recommended name:
Huntingtin-interacting protein 1
Short name:
HIP-1
Alternative name(s):
Huntingtin-interacting protein I
Short name:
HIP-I
Gene namesi
Name:HIP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000127946.16
HGNCiHGNC:4913 HIP1
MIMi601767 gene
neXtProtiNX_O00291

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

Cytoplasm, Cytoplasmic vesicle, Membrane, Nucleus

Pathology & 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 keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi56K → E: Abolishes 3-phosphoinositide-binding; when associated with E-58. 1 Publication1
Mutagenesisi58K → E: Abolishes 3-phosphoinositide-binding; when associated with E-56. 1 Publication1
Mutagenesisi432F → G: Abolishes HIP1-induced cell death. 1 Publication1
Mutagenesisi1005R → E: Reduces AR-induced nuclear translocation. 1 Publication1

Keywords - Diseasei

Neurodegeneration

Organism-specific databases

DisGeNETi3092
MalaCardsiHIP1
OpenTargetsiENSG00000127946
PharmGKBiPA29289

Polymorphism and mutation databases

BioMutaiHIP1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000839861 – 1037Huntingtin-interacting protein 1Add BLAST1037

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei338PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO00291
PaxDbiO00291
PeptideAtlasiO00291
PRIDEiO00291
ProteomicsDBi47823

PTM databases

iPTMnetiO00291
PhosphoSitePlusiO00291
SwissPalmiO00291

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

BgeeiENSG00000127946
CleanExiHS_HIP1
ExpressionAtlasiO00291 baseline and differential
GenevisibleiO00291 HS

Organism-specific databases

HPAiCAB015334
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

Show more details

GO - Molecular functioni

  • actin filament 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

BioGridi109339, 29 interactors
DIPiDIP-17041N
ELMiO00291
IntActiO00291, 37 interactors
MINTiO00291
STRINGi9606.ENSP00000336747

Structurei

Secondary structure

11037
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi373 – 441Combined sources69
Turni459 – 461Combined sources3
Helixi462 – 465Combined sources4
Helixi482 – 580Combined sources99

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2NO2X-ray2.80A482-586[»]
2QA7X-ray2.80A/B/C/D370-481[»]
3I00X-ray2.30A/B361-480[»]
ProteinModelPortaliO00291
SMRiO00291
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO00291

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini32 – 160ENTHPROSITE-ProRule annotationAdd BLAST129
Domaini771 – 1012I/LWEQPROSITE-ProRule annotationAdd BLAST242

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni410 – 491pDEDAdd BLAST82
Regioni867 – 924Important for actin bindingBy similarityAdd BLAST58

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili368 – 644Sequence analysisAdd BLAST277

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 coil

Phylogenomic databases

eggNOGiKOG0980 Eukaryota
ENOG410XRXQ LUCA
GeneTreeiENSGT00550000074542
HOGENOMiHOG000020612
HOVERGENiHBG005968
InParanoidiO00291
KOiK04559
OMAiNNRWTEG
OrthoDBiEOG091G07Y5
PhylomeDBiO00291
TreeFamiTF316860

Family and domain databases

Gene3Di1.25.40.90, 1 hit
InterProiView 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
PANTHERiPTHR10407 PTHR10407, 1 hit
PTHR10407:SF14 PTHR10407:SF14, 1 hit
PfamiView protein in Pfam
PF07651 ANTH, 1 hit
PF16515 HIP1_clath_bdg, 1 hit
PF01608 I_LWEQ, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD011820 ILWEQ, 1 hit
SMARTiView protein in SMART
SM00273 ENTH, 1 hit
SM00307 ILWEQ, 1 hit
SUPFAMiSSF109885 SSF109885, 1 hit
SSF48464 SSF48464, 1 hit
PROSITEiView protein in PROSITE
PS50942 ENTH, 1 hit
PS50945 I_LWEQ, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative 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.

« Hide

        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
Length:1,037
Mass (Da):116,221
Last modified:September 23, 2008 - v5
Checksum:iF8C0369DBF0A836F
GO
Isoform HIP1-2 (identifier: O00291-2)
Sequence is not available
Length:
Mass (Da):
Isoform 3 (identifier: O00291-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     803-853: Missing.

Note: No experimental confirmation available.
Show »
Length:986
Mass (Da):110,663
Checksum:iC09BAD680242941A
GO
Isoform 4 (identifier: O00291-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-40: MDRMASSMKQVPNPLPKVLSRRGVGAGLEAAERESFERTQ → MMFPNPEPPPE

Show »
Length:1,008
Mass (Da):113,076
Checksum:i37DDE891F2F15C00
GO

Sequence cautioni

The sequence AAC51257 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti89A → P in AAC33564 (PubMed:11788820).Curated1
Sequence conflicti245 – 251KLHSCLP → EFAAAST in CAA70574 (PubMed:9147654).Curated7
Sequence conflicti357S → R in BAG65499 (PubMed:14702039).Curated1
Sequence conflicti639 – 644LNQLEE → STRPRI in CAA70574 (PubMed:9147654).Curated6
Sequence conflicti688L → F in AAL87037 (PubMed:11788820).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051032263M → K. Corresponds to variant dbSNP:rs17149023Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0574001 – 40MDRMA…FERTQ → MMFPNPEPPPE in isoform 4. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_044736803 – 853Missing in isoform 3. 1 PublicationAdd BLAST51

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
CCDSiCCDS34669.1 [O00291-1]
CCDS59060.1 [O00291-3]
RefSeqiNP_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]
UniGeneiHs.329266
Hs.619089
Hs.674397

Genome annotation databases

EnsembliENST00000336926; ENSP00000336747; ENSG00000127946 [O00291-1]
ENST00000434438; ENSP00000410300; ENSG00000127946 [O00291-3]
ENST00000616821; ENSP00000484528; ENSG00000127946 [O00291-4]
GeneIDi3092
KEGGihsa:3092
UCSCiuc003uds.4 human [O00291-1]
uc064emn.1 human

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHIP1_HUMAN
AccessioniPrimary (citable) accession number: O00291
Secondary accession number(s): B4E3I7
, E7ES17, O00328, Q2TB58, Q8TDL4, V5LU97
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 27, 2001
Last sequence update: September 23, 2008
Last modified: June 20, 2018
This is version 186 of the entry and version 5 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

Documents

  1. Human chromosome 7
    Human chromosome 7: 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

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