HAP1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: HAP1_MOUSE
• UniProt AC: O35668
• Protein Name: Huntingtin-associated protein 1
• Gene Name: Hap1
• Organism: Mus musculus (Mouse).
• Sequence Length: 628
• 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 c
• 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 regulating the number of Npyr1-expressing cells), 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 ciliogenesiss; however, reports are conflicting: PubMed:21985783 reports that Hap1 is required for ciliogenesis in primary cortical neurons and proposes that HTT interacts with PCM1 through HAP1; PubMed:23532844 reports that mice with disrupted Hap1 display normal cilium formation and function. Involved in regulation of exocytosis. Isoform A but not isoform B 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..
• Protein Sequence: MRPKEQVQSGAGDGTGSGDPAAGTPTTQPAVGPAPEPSAEPKPAPAQGTGSGQKSGSRTKTGSFCRSMIIGDSDAPWTRYVFQGPYGPRATGLGTGKAEGIWKTPAAYIGRRPGVSGPERAAFIRELQEALCPNPPPTKKITEDDVKVMLYLLEEKERDLNTAARIGQSLVKQNSVLMEENNKLETMLGSAREEILHLRKQVNLRDDLLQLYSDSDDDDDEEDEEDEEEGEEEEREGQRDQDQQHDHPYGAPKPHPKAETAHRCPQLETLQQKLRLLEEENDHLREEASHLDNLEDEEQMLILECVEQFSEASQQMAELSEVLVLRLEGYERQQKEITQLQAEITKLQQRCQSYGAQTEKLQQMLASEKGIHSESLRAGSYMQDYGSRPRDRQEDGKSHRQRSSMPAGSVTHYGYSVPLDALPSFPETLAEELRTSLRKFITDPAYFMERRDTHCREGRKKEQRAMPPPPAQDLKPPEDFEAPEELVPEEELGAIEEVGTAEDGQAEENEQASEETEAWEEVEPEVDETTRMNVVVSALEASGLGPSHLDMKYVLQQLSNWQDAHSKRQQKQKVVPKDSPTPQQQTNMGGGILEQQPRVPTQDSQRLEEDRATHSPSAREEEGPSGAT

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
49	Phosphorylation	KPAPAQGTGSGQKSG CCCCCCCCCCCCCCC	18.98	28066266
51	Phosphorylation	APAQGTGSGQKSGSR CCCCCCCCCCCCCCC	37.58	28066266
67	Phosphorylation	KTGSFCRSMIIGDSD CCCCCCCCEEECCCC	18.60	28066266
89	Methylation	FQGPYGPRATGLGTG ECCCCCCCCCCCCCC	40.18	-
104	Phosphorylation	KAEGIWKTPAAYIGR CCCCCCCCCHHHCCC	11.81	26026062
175	Phosphorylation	QSLVKQNSVLMEENN HHHHHHCCEECCCCC	17.71	25521595
213	Phosphorylation	DDLLQLYSDSDDDDD HHHHHHHCCCCCCCC	38.95	29899451
215	Phosphorylation	LLQLYSDSDDDDDEE HHHHHCCCCCCCCCC	36.68	29899451
273	Ubiquitination	QLETLQQKLRLLEEE HHHHHHHHHHHHHHH	23.71	22790023
346	Ubiquitination	QLQAEITKLQQRCQS HHHHHHHHHHHHHHH	50.38	22790023
369	Ubiquitination	QQMLASEKGIHSESL HHHHHHCCCCCCHHH	61.75	22790023
373	Phosphorylation	ASEKGIHSESLRAGS HHCCCCCCHHHHHCC	27.28	28066266
375	Phosphorylation	EKGIHSESLRAGSYM CCCCCCHHHHHCCCC	26.60	28066266
413	Phosphorylation	PAGSVTHYGYSVPLD CCCCCCCCCEECCHH	14.37	-
439	Ubiquitination	ELRTSLRKFITDPAY HHHHHHHHHHCCHHH	46.54	22790023
440	Ubiquitination	LRTSLRKFITDPAYF HHHHHHHHHCCHHHH	6.17	27667366
537	Phosphorylation	TRMNVVVSALEASGL HHHHHHHHHHHHCCC	18.61	25777480
542	Phosphorylation	VVSALEASGLGPSHL HHHHHHHCCCCCCHH	25.77	25777480
547	Phosphorylation	EASGLGPSHLDMKYV HHCCCCCCHHCHHHH	34.58	25777480
567	Ubiquitination	NWQDAHSKRQQKQKV CHHHHHHHHHHHCCC	44.34	22790023
579	Phosphorylation	QKVVPKDSPTPQQQT CCCCCCCCCCHHHHC	36.48	29899451
581	Phosphorylation	VVPKDSPTPQQQTNM CCCCCCCCHHHHCCC	37.37	25521595
586	Phosphorylation	SPTPQQQTNMGGGIL CCCHHHHCCCCCCHH	23.88	30635358
598 (in isoform 2)	Phosphorylation	-	42.59	-
601	Phosphorylation	EQQPRVPTQDSQRLE CCCCCCCCCCHHHHH	42.00	-
604	Phosphorylation	PRVPTQDSQRLEEDR CCCCCCCHHHHHHHH	13.84	29899451
613	Phosphorylation	RLEEDRATHSPSARE HHHHHHCCCCCCHHC	24.63	29899451
615	Phosphorylation	EEDRATHSPSAREEE HHHHCCCCCCHHCCC	19.05	25521595
617	Phosphorylation	DRATHSPSAREEEGP HHCCCCCCHHCCCCC	42.86	29899451
628	Phosphorylation	EEGPSGAT------- CCCCCCCC-------	42.54	29899451

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

Oops, there are no upstream regulatory protein records of HAP1_MOUSE !!

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
598	T	Phosphorylation	Isoform A is phosphorylated on Thr-598.	-

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_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference

Drug and Disease Associations

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