dbPTM

HCK_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	HCK_HUMAN
UniProt AC	P08631
Protein Name	Tyrosine-protein kinase HCK
Gene Name	HCK
Organism	Homo sapiens (Human).
Sequence Length	526
Subcellular Localization	Isoform 1: Lysosome. Membrane Lipid-anchor. Cell projection, podosome membrane Lipid-anchor. Cytoplasm, cytosol. Associated with specialized secretory lysosomes called azurophil granules. At least half of this isoform is found in the cytoplasm, som
Protein Description	Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS..
Protein Sequence	MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIKPGPNSHNSNTPGIREAGSEDIIVVALYDYEAIHHEDLSFQKGDQMVVLEESGEWWKARSLATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSYSLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYNIMMRCWKNRPEERPTFEYIQSVLDDFYTATESQYQQQP

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	N-myristoyl glycine	------MGGRSSCED ------CCCCCCCCC	39.97	-
2	Myristoylation	------MGGRSSCED ------CCCCCCCCC	39.97	7791757
2 (in isoform 2)	Myristoylation	-	39.97	7791757
3 (in isoform 2)	S-palmitoylation	-	25.62	7791757
3	S-palmitoylation	-----MGGRSSCEDP -----CCCCCCCCCC	25.62	7791757
7	Ubiquitination	-MGGRSSCEDPGCPR -CCCCCCCCCCCCCC	7.88	21890473
7 (in isoform 2)	Ubiquitination	-	7.88	21890473
27	Phosphorylation	PRMGCMKSKFLQVGG CCCCCCCCCEEEECC	11.19	29759185
28 (in isoform 1)	Ubiquitination	-	44.57	21890473
28	Ubiquitination	RMGCMKSKFLQVGGN CCCCCCCCEEEECCE	44.57	21890473
36	Phosphorylation	FLQVGGNTFSKTETS EEEECCEECCCCCCC	32.34	28674151
38	Phosphorylation	QVGGNTFSKTETSAS EECCEECCCCCCCCC	36.31	30108239
40	Phosphorylation	GGNTFSKTETSASPH CCEECCCCCCCCCCC	43.21	28176486
42	Phosphorylation	NTFSKTETSASPHCP EECCCCCCCCCCCCC	34.52	28176486
43	Phosphorylation	TFSKTETSASPHCPV ECCCCCCCCCCCCCE	22.10	28176486
45	Phosphorylation	SKTETSASPHCPVYV CCCCCCCCCCCCEEC	18.23	28176486
51	Phosphorylation	ASPHCPVYVPDPTST CCCCCCEECCCCCCC	7.45	27155012
56	Phosphorylation	PVYVPDPTSTIKPGP CEECCCCCCCCCCCC	45.97	28176486
57	Phosphorylation	VYVPDPTSTIKPGPN EECCCCCCCCCCCCC	33.26	28857561
58	Phosphorylation	YVPDPTSTIKPGPNS ECCCCCCCCCCCCCC	35.18	28857561
89	Phosphorylation	IVVALYDYEAIHHED EEEEEECHHHCCCCC	8.16	-
103 (in isoform 2)	Ubiquitination	-	40.20	21890473
103	Ubiquitination	DLSFQKGDQMVVLEE CCCCCCCCEEEEEEE	40.20	21890473
111	Phosphorylation	QMVVLEESGEWWKAR EEEEEEECCCHHHHH	32.41	27251275
119	Phosphorylation	GEWWKARSLATRKEG CCHHHHHHHHCCCCC	27.50	21406692
122	Phosphorylation	WKARSLATRKEGYIP HHHHHHHCCCCCCCC	47.79	21406692
124 (in isoform 1)	Ubiquitination	-	51.65	21890473
124	Ubiquitination	ARSLATRKEGYIPSN HHHHHCCCCCCCCCC	51.65	21890473
127	Phosphorylation	LATRKEGYIPSNYVA HHCCCCCCCCCCCEE	15.68	19369195
176	Phosphorylation	MIRDSETTKGSYSLS EEECCCCCCCEEEEE	29.38	28857561
179	Phosphorylation	DSETTKGSYSLSVRD CCCCCCCEEEEEEEE	17.07	28060719
180	Phosphorylation	SETTKGSYSLSVRDY CCCCCCEEEEEEEEC	23.46	30108239
181	Phosphorylation	ETTKGSYSLSVRDYD CCCCCEEEEEEEECC	18.83	30108239
183	Phosphorylation	TKGSYSLSVRDYDPR CCCEEEEEEEECCCC	14.79	30108239
202	Phosphorylation	VKHYKIRTLDNGGFY EEEEEEEECCCCCEE	41.77	28450419
209	Phosphorylation	TLDNGGFYISPRSTF ECCCCCEEECCCCCH	12.08	27155012
211	Phosphorylation	DNGGFYISPRSTFST CCCCEEECCCCCHHH	11.68	28442448
214	Phosphorylation	GFYISPRSTFSTLQE CEEECCCCCHHHHHH	36.87	24247654
228	Acetylation	ELVDHYKKGNDGLCQ HHHHHHHHCCCCCCH	56.64	30589129
238	Phosphorylation	DGLCQKLSVPCMSSK CCCCHHCCCCCCCCC	30.92	-
261	Phosphorylation	AWEIPRESLKLEKKL CCCCCHHHHHHHHHH	31.89	24247654
283	Ubiquitination	VWMATYNKHTKVAVK EEEEECCCCCCEEEE	42.09	-
286	Ubiquitination	ATYNKHTKVAVKTMK EECCCCCCEEEEECC	28.10	-
291	Phosphorylation	HTKVAVKTMKPGSMS CCCEEEEECCCCCEE	24.67	21406692
296	Phosphorylation	VKTMKPGSMSVEAFL EEECCCCCEEHHHHH	19.19	21406692
298	Phosphorylation	TMKPGSMSVEAFLAE ECCCCCEEHHHHHHH	20.64	21406692
311	Phosphorylation	AEANVMKTLQHDKLV HHHCHHHHHCCCCCE	17.35	-
330	Phosphorylation	VVTKEPIYIITEFMA EEECCCEEEEEEHHH	9.29	19060867
340	Phosphorylation	TEFMAKGSLLDFLKS EEHHHCCCHHHHHHC	25.67	27251275
347	O-linked_Glycosylation	SLLDFLKSDEGSKQP CHHHHHHCCCCCCCC	42.94	29351928
351	O-linked_Glycosylation	FLKSDEGSKQPLPKL HHHCCCCCCCCCCHH	26.52	29351928
411	Phosphorylation	RVIEDNEYTAREGAK EEECCCCEECCCCCC	16.38	19664994
412	Phosphorylation	VIEDNEYTAREGAKF EECCCCEECCCCCCC	17.04	21945579
418	Ubiquitination	YTAREGAKFPIKWTA EECCCCCCCCCEECC	63.63	-
442	Phosphorylation	TIKSDVWSFGILLME EECHHHHHHHHHEEE	17.28	-
462	Phosphorylation	RIPYPGMSNPEVIRA CCCCCCCCCHHHHHH	55.97	19060867
503	Phosphorylation	NRPEERPTFEYIQSV CCCCCCCCHHHHHHH	35.01	30301811
506	Phosphorylation	EERPTFEYIQSVLDD CCCCCHHHHHHHHHH	10.48	30301811
509	Phosphorylation	PTFEYIQSVLDDFYT CCHHHHHHHHHHHHH	18.32	30301811
515	Phosphorylation	QSVLDDFYTATESQY HHHHHHHHHHHHHHH	11.49	20860994
516	Phosphorylation	SVLDDFYTATESQYQ HHHHHHHHHHHHHHH	27.39	30301811
518	Phosphorylation	LDDFYTATESQYQQQ HHHHHHHHHHHHHCC	28.50	28450419
520	Phosphorylation	DFYTATESQYQQQP- HHHHHHHHHHHCCC-	29.81	28450419
522	Phosphorylation	YTATESQYQQQP--- HHHHHHHHHCCC---	19.98	21082442

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

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
209	Y	Phosphorylation	Kinase	HCK	P08631	PhosphoELM
411	Y	Phosphorylation	Kinase	CHEK1	O14757	GPS
411	Y	Phosphorylation	Kinase	CSK	P41240	PSP
411	Y	Phosphorylation	Kinase	HCK	P08631	PSP
411	Y	Phosphorylation	Kinase	AXL	P30530	PSP
522	Y	Phosphorylation	Kinase	HCK	P08631	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of HCK_HUMAN !!

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of HCK_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
RPGF1_HUMAN	RAPGEF1	physical	14551197
ELMO1_HUMAN	ELMO1	physical	12029088
WIPF1_HUMAN	WIPF1	physical	12029088
WASP_HUMAN	WAS	physical	12029088
CBL_HUMAN	CBL	physical	10092522
SKAP2_HUMAN	SKAP2	physical	9837776
PECA1_HUMAN	PECAM1	physical	10858437
CSF3R_HUMAN	CSF3R	physical	9790917
ADA15_HUMAN	ADAM15	physical	11741929
IL6RB_HUMAN	IL6ST	physical	11689697
RL10_HUMAN	RPL10	physical	12138090
RASA3_HUMAN	RASA3	physical	7782336
RASA1_HUMAN	RASA1	physical	7782336
NEF_HV1H2	nef	physical	18042718
NEF_HV1H2	nef	physical	9778343
SRC_HUMAN	SRC	physical	11896602
KHDR1_HUMAN	KHDRBS1	physical	22745667
SH3K1_HUMAN	SH3KBP1	physical	15707590
CBP_HUMAN	CREBBP	physical	22364282
ACK1_HUMAN	TNK2	physical	14506255
NEF_HV1H2	nef	physical	21886773
CBL_HUMAN	CBL	physical	8995358
A4_HUMAN	APP	physical	21832049
ACTB_HUMAN	ACTB	physical	17868192
RUFY1_HUMAN	RUFY1	physical	17868192
ERBB3_HUMAN	ERBB3	physical	16273093
WNT2_HUMAN	WNT2	physical	21988832
SPR2A_HUMAN	SPRR2A	physical	18155796
MTUS2_HUMAN	MTUS2	physical	25416956
GOPC_HUMAN	GOPC	physical	25416956
K1C40_HUMAN	KRT40	physical	25416956
KR109_HUMAN	KRTAP10-9	physical	25416956
NT2NL_HUMAN	NOTCH2NL	physical	25416956
MDM2_HUMAN	MDM2	physical	25624478
NGEF_HUMAN	NGEF	physical	25814554
P55G_HUMAN	PIK3R3	physical	25814554
FRS3_HUMAN	FRS3	physical	25814554
LTMD1_HUMAN	LETMD1	physical	25814554
OLIG1_HUMAN	OLIG1	physical	25814554
FAK1_HUMAN	PTK2	physical	25814554
GRB14_HUMAN	GRB14	physical	25814554
PK3CB_HUMAN	PIK3CB	physical	25241761

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.

Regulatory Network of HCK_HUMAN

Related Literatures of Post-Translational Modification

Myristoylation
Reference	PubMed
"Myristoylation and differential palmitoylation of the HCK protein-tyrosine kinases govern their attachment to membranes and associationwith caveolae."; Robbins S.M., Quintrell N.A., Bishop J.M.; Mol. Cell. Biol. 15:3507-3515(1995). Cited for: SUBCELLULAR LOCATION, ALTERNATIVE INITIATION, MYRISTOYLATION,PALMITOYLATION, AND MUTAGENESIS OF GLY-3; GLY-23 AND CYS-24.	7791757 [Abstract]
Phosphorylation
Reference	PubMed
"Large-scale proteomics analysis of the human kinome."; Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.; Mol. Cell. Proteomics 8:1751-1764(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-36; TYR-51; TYR-127;THR-202; TYR-209; TYR-330; TYR-411; SER-462; TYR-515; SER-520 ANDTYR-522, AND MASS SPECTROMETRY.	19369195 [Abstract]
"Discovery of A-770041, a src-family selective orally active lckinhibitor that prevents organ allograft rejection."; Burchat A., Borhani D.W., Calderwood D.J., Hirst G.C., Li B.,Stachlewitz R.F.; Bioorg. Med. Chem. Lett. 16:118-122(2006). Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 81-522 IN COMPLEXES WITHINHIBITORS A-420983; A-641359 AND A-770041, ENZYME REGULATION, ANDPHOSPHORYLATION AT TYR-522.	16216497 [Abstract]
"Crystal structure of Hck in complex with a Src family-selectivetyrosine kinase inhibitor."; Schindler T., Sicheri F., Pico A., Gazit A., Levitzki A., Kuriyan J.; Mol. Cell 3:639-648(1999). Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 81-522 IN COMPLEX WITH THEPYRAZOLO PYRIMIDINE-TYPE INHIBITOR PP1, AND PHOSPHORYLATION ATTYR-522.	10360180 [Abstract]
"Crystal structure of the Src family tyrosine kinase Hck."; Sicheri F., Moarefi I., Kuriyan J.; Nature 385:602-609(1997). Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 78-526 IN COMPLEX WITHCALCIUM, AND PHOSPHORYLATION AT TYR-522.	9024658 [Abstract]
"Phosphoproteome of resting human platelets."; Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,Schuetz C., Walter U., Gambaryan S., Sickmann A.; J. Proteome Res. 7:526-534(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-411, AND MASSSPECTROMETRY.	18088087 [Abstract]
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer."; Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; Cell 131:1190-1203(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-209, AND MASSSPECTROMETRY.	18083107 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-411, AND MASSSPECTROMETRY.	17081983 [Abstract]
"Membrane-anchored Cbl suppresses Hck protein-tyrosine kinase mediatedcellular transformation."; Howlett C.J., Robbins S.M.; Oncogene 21:1707-1716(2002). Cited for: FUNCTION IN CELL PROLIFERATION, UBIQUITINATION, PHOSPHORYLATION ATTYR-51; TYR-411 AND TYR-522, SUBCELLULAR LOCATION, INTERACTION WITHCBL (ISOFORM 2), AND MUTAGENESIS OF LYS-290 AND TYR-522.	11896602 [Abstract]
"Reciprocal regulation of Hck activity by phosphorylation of Tyr(527)and Tyr(416). Effect of introducing a high affinity intramolecular SH2ligand."; Porter M., Schindler T., Kuriyan J., Miller W.T.; J. Biol. Chem. 275:2721-2726(2000). Cited for: PHOSPHORYLATION AT TYR-411 AND TYR-522, MASS SPECTROMETRY, ENZYMEREGULATION, AND MUTAGENESIS OF GLU-305 AND TYR-411.	10644735 [Abstract]