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FLASH GENE

Symbol

HIP1

contributors: mct - updated : 27-04-2012

HGNC name	huntingtin interacting protein 1
HGNC id	4913

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	DEL7Q1123 chromosome 7q11.23 microdeletion, distally adjacent to WBS common deletion
Location	7q11.23      Physical location : 75.163.408 - 75.368.279
Synonym symbol(s)	ILWEQ, MGC126506

DNA

TYPE	functioning gene
STRUCTURE	204.00 kb     31 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	a clathrin-box and AP2 consensus-binding sites that display high affinity binding to the terminal domain of the clathrin heavy chain and the ear domain of the AP2 alpha subunit, respectively

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005338 31 - 8051 NP_005329 115.4 1030 - 2005 15533941 NM_001243198 - - 7898 NP_001230127 - 1003 - 2005 15533941

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic spleen         Digestive liver         Nervous brain       predominantly Reproductive male system testis       Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Lymphoid         Nervous central       Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens Reproductive spermatid

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	four-tyrosine "HIP1 phosphorylation motif" (HPM) in the N-terminal region required for phosphorylation mediated by both EGFR and PDGFRB
	ENTH domain (epsin N terminal homology)
	copies of the sequence motif DPF (Asp-Pro-Phe)
	coiled coil forming domain containing a potential clathrin binding motif, and is potentially uniquely suited to allow conformational flexibility
	talin like actin-binding domain, TALIN homology domains that have the capacity to interact with actin

HOMOLOGY

interspecies	homolog to yeast S. cerevisiae Sla2p or End4p,Mop2p
	ortholog to murine Hip1 hutingtin interacting protein 1

Homologene

FAMILY

SLA2 family

CATEGORY

structural protein , transport

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic,vesicle
	intracellular,nucleus
text	associated with the clathrin coated vesicles
	highly colocalized with clathrin at the plasma membrane and shares similar dynamics with a subpopulation of clathrin assemblies
	postsynaptic HIP1 is concentrated near the plasma membrane

basic FUNCTION	putatively involved in endocytosis and synaptic vesicle recycling in neurons
	may be playing a fundamental role in clathrin trafficking
	required for the survival /proliferation of diverses types of somatic cells including hematopoietic progenitors
	regulating clathrin assembly through direct binding to the regulatory region of the clathrin light chain
	EPN1 and huntingtin-interacting protein 1 (HIP1) are endocytic accessory proteins
	EPN1 and HIP1 in the synapse: as broadly required factors for promoting clathrin assembly and as adaptors for specific endocytic pathways
	playing roles with HIP1R in affecting clathrin assembly and actin distribution are mediated by their interaction with the conserved sequence of clathrin light chains
	plays a key role in endocytosis and intracellular transport, and in Notch-mediated neurogenesis
	accessory protein of the clathrin-mediated endocytosis (CME) pathway
	role in pits maturation and formation of the coated vesicle, and having strong dependence on clathrin for membranal localization
	important link between the actin cytoskeleton and clathrin-mediated endocytosis machinery

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

endocytosis transport

PATHWAY

metabolism

signaling

a component	component of clathrin coats
	EFT57/HIP1 heterodimer recruits procaspase-8, followed by its activation and induction of the downstream apoptotic cascade

INTERACTION

DNA

RNA

small molecule

protein	huntingtin, clathrin, AP2 (adaptor protein 2), playing a functinal role in clathrin-mediated endocytosis
	clathrin heavy chain 1, alpha adaptin A CLAPA1 and alpha adaptin CL, AP2A2
	actin binding by HIP1 and HIP1R is regulated by clathrin light chain
	binding of HIP1 to actin is regulated through an interaction with clathrin light chain
	interacts with SCF-activated KIT
	proapoptotic protein that preferentially interacts with wild type HTT, but under diseased conditions when HTT is mutated, HIP1 dissociates from mutant HTT and interacts with IFT57

cell & other

REGULATION

Phosphorylated by

receptor tyrosine kinases (RTKs) and phosphorylation of HIP1 by RTKs in an N-terminal region contributes to the promotion of cellular survival (pMID: 23836884)

Other

huntingtin polyglutamine expansion liberates (heterodimer with ESRRBL1 and CASP8 favoured)

ASSOCIATED DISORDERS

corresponding disease(s)

DEL7Q1123

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral fusion translocation   protein chimeric t(5;7)(q33;q11.2) in chronic myelomonocytic leukemia leading to a HIP1-PDGFRB gene fusion tumoral     --over   in multiple tumors(prostate and colon tumor) constitutional     --over   in fibroblasts from progeria patients and elderly individuals tumoral     --over   in Merkel cell carcinoma constitutional     --over   increases levels of the RTK epidermal growth factor receptor (EGFR) and transforms fibroblasts

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS