HAP1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: HAP1_HUMAN
• UniProt AC: P54257
• Protein Name: Huntingtin-associated protein 1
• Gene Name: HAP1
• Organism: Homo sapiens (Human).
• Sequence Length: 671
• Subcellular Localization: Cytoplasm . Cell projection, axon . Cytoplasm, cytoskeleton. Lysosome. Endoplasmic reticulum. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle. Mitochondrion . Nucleus. Cytoplasmic vesicle, autophagosome. Localizes to large nonmembrane-bound
• Protein Description: Originally identified as neuronal protein that specifically associates with HTT/huntingtin and the binding is enhanced by an expanded polyglutamine repeat within HTT possibly affecting HAP1 interaction properties. Both HTT and HAP1 are involved in intracellular trafficking and HAP1 is proposed to link HTT to motor proteins and/or transport cargos. Seems to play a role in vesicular transport within neurons and axons such as from early endosomes to late endocytic compartments and to promote neurite outgrowth. The vesicular transport function via association with microtubule-dependent transporters can be attenuated by association with mutant HTT. Involved in the axonal transport of BDNF and its activity-dependent secretion; the function seems to involve HTT, DCTN1 and a complex with SORT1. Involved in APP trafficking and seems to facilitate APP anterograde transport and membrane insertion thereby possibly reducing processing into amyloid beta. Involved in delivery of gamma-aminobutyric acid (GABA(A)) receptors to synapses; the function is dependent on kinesin motor protein KIF5 and is disrupted by HTT with expanded polyglutamine repeat. Involved in regulation of autophagosome motility by promoting efficient retrograde axonal transport. Seems to be involved in regulation of membrane receptor recycling and degradation, and respective signal transduction, including GABA(A) receptors, tyrosine kinase receptors, EGFR, IP3 receptor and androgen receptor. Among others suggested to be involved in control of feeding behavior (involving hypothalamic GABA(A) receptors), cerebellar and brainstem development (involving AHI1 and NTRK1/TrkA), postnatal neurogenesis (involving hypothalamic NTRK2/TrkB), and ITPR1/InsP3R1-mediated Ca(2+) release (involving HTT and possibly the effect of mutant HTT). Via association with DCTN1/dynactin p150-glued and HTT/huntingtin involved in cytoplasmic retention of REST in neurons. May be involved in ciliogenesis. Involved in regulation of exocytosis. Seems to be involved in formation of cytoplasmic inclusion bodies (STBs). In case of anomalous expression of TBP, can sequester a subset of TBP into STBs; sequestration is enhanced by an expanded polyglutamine repeat within TBP. HAP1-containing STBs have been proposed to play a protective role against neurodegeneration in Huntigton disease (HD) and spinocerebellar ataxia 17 (SCA17)..
• Protein Sequence: MRPKRLGRCCAGSRLGPGDPAALTCAPSPSASPAPEPSAQPQARGTGQRVGSRATSGSQFLSEARTGARPASEAGAKAGARRPSAFSAIQGDVRSMPDNSDAPWTRFVFQGPFGSRATGRGTGKAAGIWKTPAAYVGRRPGVSGPERAAFIRELEEALCPNLPPPVKKITQEDVKVMLYLLEELLPPVWESVTYGMVLQRERDLNTAARIGQSLVKQNSVLMEENSKLEALLGSAKEEILYLRHQVNLRDELLQLYSDSDEEDEDEEEEEEEKEAEEEQEEEEAEEDLQCAHPCDAPKLISQEALLHQHHCPQLEALQEKLRLLEEENHQLREEASQLDTLEDEEQMLILECVEQFSEASQQMAELSEVLVLRLENYERQQQEVARLQAQVLKLQQRCRMYGAETEKLQKQLASEKEIQMQLQEESVWVGSQLQDLREKYMDCGGMLIEMQEEVKTLRQQPPVSTGSATHYPYSVPLETLPGFQETLAEELRTSLRRMISDPVYFMERNYEMPRGDTSSLRYDFRYSEDREQVRGFEAEEGLMLAADIMRGEDFTPAEEFVPQEELGAAKKVPAEEGVMEEAELVSEETEGWEEVELELDEATRMNVVTSALEASGLGPSHLDMNYVLQQLANWQDAHYRRQLRWKMLQKGECPHGALPAASRTSCRSSCR

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
38	Phosphorylation	ASPAPEPSAQPQARG CCCCCCCCCCCCCCC	37.56	22468782
72	Phosphorylation	RTGARPASEAGAKAG HCCCCCHHHHHHHHC	30.57	24144214
401	Phosphorylation	LQQRCRMYGAETEKL HHHHHHHCCHHHHHH	8.20	26437602
440	Phosphorylation	LQDLREKYMDCGGML HHHHHHHHHCCCCHH	8.07	22817900
504	Phosphorylation	RMISDPVYFMERNYE HHHCCHHHHHHCCCC	11.55	29759185
662	Phosphorylation	HGALPAASRTSCRSS CCCCCCCCCHHHHHH	37.89	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Oops, there are no upstream regulatory protein records of HAP1_HUMAN !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of HAP1_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of HAP1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
HD_HUMAN	HTT	physical	7477378
DCTN1_HUMAN	DCTN1	physical	9454836
HGS_HUMAN	HGS	physical	12021262
HD_HUMAN	HTT	physical	9454836
HAP1_HUMAN	HAP1	physical	9798945
DCTN1_HUMAN	DCTN1	physical	9361024
HAP1_HUMAN	HAP1	physical	9361024
PCM1_HUMAN	PCM1	physical	9361024
HD_HUMAN	HTT	physical	9668110
HSP74_HUMAN	HSPA4	physical	11133992
HD_HUMAN	HTT	physical	15383276
GIT1_HUMAN	GIT1	physical	15383276
KAT7_HUMAN	KAT7	physical	15383276
KAT5_HUMAN	KAT5	physical	15383276
FEZ1_HUMAN	FEZ1	physical	15383276
LRIF1_HUMAN	LRIF1	physical	15383276
HAP1_HUMAN	HAP1	physical	15383276
KBTB7_HUMAN	KBTBD7	physical	15383276
ING5_HUMAN	ING5	physical	15383276
GASP2_HUMAN	GPRASP2	physical	15383276

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.