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UniProtKB - O00291 (HIP1_HUMAN)

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Protein

Huntingtin-interacting protein 1

Gene

HIP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
Complete GO annotation...

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
Complete GO annotation...

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-8856828. Clathrin-mediated endocytosis.
SIGNORiO00291.

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:4913. HIP1.

Subcellular locationi

GO - Cellular componenti

  • clathrin-coated vesicle Source: UniProtKB
  • clathrin-coated vesicle membrane Source: UniProtKB-SubCell
  • cytoplasm Source: MGI
  • cytoskeleton Source: ProtInc
  • cytosol Source: Reactome
  • extrinsic component of cytoplasmic side of plasma membrane Source: Ensembl
  • extrinsic component of postsynaptic membrane Source: Ensembl
  • extrinsic component of presynaptic membrane Source: Ensembl
  • Golgi apparatus Source: MGI
  • intracellular membrane-bounded organelle Source: HPA
  • membrane Source: ProtInc
  • nucleus Source: ParkinsonsUK-UCL
  • postsynapse Source: ParkinsonsUK-UCL
  • presynapse Source: ParkinsonsUK-UCL
Complete GO annotation...

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.

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
  • 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
Complete GO annotation...

Protein-protein interaction databases

BioGridi109339. 27 interactors.
DIPiDIP-17041N.
IntActiO00291. 36 interactors.
MINTiMINT-208214.
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.
IPR002558. ILWEQ_dom.
IPR030224. Sla2_fam.
PANTHERiPTHR10407. PTHR10407. 1 hit.
PTHR10407:SF18. PTHR10407:SF18. 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

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.

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 7, 2017
This is version 179 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