dbPTM

CXA1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	CXA1_HUMAN
UniProt AC	P17302
Protein Name	Gap junction alpha-1 protein
Gene Name	GJA1
Organism	Homo sapiens (Human).
Sequence Length	382
Subcellular Localization	Cell membrane Multi-pass membrane protein . Cell junction, gap junction . Endoplasmic reticulum . Localizes at the intercalated disk (ICD) in cardiomyocytes and the proper localization at ICD is dependent on TMEM65.
Protein Description	Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract (By similarity). May play a role in cell growth inhibition through the regulation of NOV expression and localization. Plays an essential role in gap junction communication in the ventricles (By similarity)..
Protein Sequence	MGDWSALGKLLDKVQAYSTAGGKVWLSVLFIFRILLLGTAVESAWGDEQSAFRCNTQQPGCENVCYDKSFPISHVRFWVLQIIFVSVPTLLYLAHVFYVMRKEEKLNKKEEELKVAQTDGVNVDMHLKQIEIKKFKYGIEEHGKVKMRGGLLRTYIISILFKSIFEVAFLLIQWYIYGFSLSAVYTCKRDPCPHQVDCFLSRPTEKTIFIIFMLVVSLVSLALNIIELFYVFFKGVKDRVKGKSDPYHATSGALSPAKDCGSQKYAYFNGCSSPTAPLSPMSPPGYKLVTGDRNNSSCRNYNKQASEQNWANYSAEQNRMGQAGSTISNSHAQPFDFPDDNQNSKKLAAGHELQPLAIVDQRPSSRASSRASSRPRPDDLEI

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
5	Phosphorylation	---MGDWSALGKLLD ---CCCHHHHHHHHH	20.53	-
9	Ubiquitination	GDWSALGKLLDKVQA CCHHHHHHHHHHHHH	46.88	21890473
109	Ubiquitination	KEEKLNKKEEELKVA HHHHHCHHHHHHHHH	70.10	-
114	Ubiquitination	NKKEEELKVAQTDGV CHHHHHHHHHHCCCC	38.51	-
128	Ubiquitination	VNVDMHLKQIEIKKF CCCHHEEEEEEEEEC	34.25	-
136	Ubiquitination	QIEIKKFKYGIEEHG EEEEEECCCCHHHCC	51.99	-
137	Phosphorylation	IEIKKFKYGIEEHGK EEEEECCCCHHHCCC	26.86	28348404
144	Ubiquitination	YGIEEHGKVKMRGGL CCHHHCCCEEECCHH	40.36	-
144	Sumoylation	YGIEEHGKVKMRGGL CCHHHCCCEEECCHH	40.36	22411987
148	Methylation	EHGKVKMRGGLLRTY HCCCEEECCHHHHHH	30.25	-
237	Sumoylation	YVFFKGVKDRVKGKS HHHHHCCHHHHCCCC	48.78	22411987
243	Ubiquitination	VKDRVKGKSDPYHAT CHHHHCCCCCCCCCC	46.07	-
244	Phosphorylation	KDRVKGKSDPYHATS HHHHCCCCCCCCCCC	53.11	-
247	Phosphorylation	VKGKSDPYHATSGAL HCCCCCCCCCCCCCC	14.74	21082442
250	Phosphorylation	KSDPYHATSGALSPA CCCCCCCCCCCCCCC	17.87	23403867
251	Phosphorylation	SDPYHATSGALSPAK CCCCCCCCCCCCCCH	23.89	19664994
255	Phosphorylation	HATSGALSPAKDCGS CCCCCCCCCCHHHCC	23.44	19664994
258	Ubiquitination	SGALSPAKDCGSQKY CCCCCCCHHHCCCCE	57.86	-
262	Phosphorylation	SPAKDCGSQKYAYFN CCCHHHCCCCEEEEC	29.81	22737133
264	Ubiquitination	AKDCGSQKYAYFNGC CHHHCCCCEEEECCC	33.28	-
265	Phosphorylation	KDCGSQKYAYFNGCS HHHCCCCEEEECCCC	10.01	11514593
267	Phosphorylation	CGSQKYAYFNGCSSP HCCCCEEEECCCCCC	8.42	22199227
271	S-nitrosocysteine	KYAYFNGCSSPTAPL CEEEECCCCCCCCCC	3.69	-
271	S-nitrosylation	KYAYFNGCSSPTAPL CEEEECCCCCCCCCC	3.69	-
272	Phosphorylation	YAYFNGCSSPTAPLS EEEECCCCCCCCCCC	40.53	22199227
273	Phosphorylation	AYFNGCSSPTAPLSP EEECCCCCCCCCCCC	30.28	22199227
275	Phosphorylation	FNGCSSPTAPLSPMS ECCCCCCCCCCCCCC	42.74	22199227
279	Phosphorylation	SSPTAPLSPMSPPGY CCCCCCCCCCCCCCC	19.93	22737133
282	Phosphorylation	TAPLSPMSPPGYKLV CCCCCCCCCCCCEEC	31.18	15605363
286	Phosphorylation	SPMSPPGYKLVTGDR CCCCCCCCEECCCCC	13.61	22199227
287	Ubiquitination	PMSPPGYKLVTGDRN CCCCCCCEECCCCCC	42.25	-
290	Phosphorylation	PPGYKLVTGDRNNSS CCCCEECCCCCCCHH	43.74	30266825
296	Phosphorylation	VTGDRNNSSCRNYNK CCCCCCCHHCCCCCH	34.07	30266825
297	Phosphorylation	TGDRNNSSCRNYNKQ CCCCCCHHCCCCCHH	21.15	30266825
301	Phosphorylation	NNSSCRNYNKQASEQ CCHHCCCCCHHHHHC	12.37	23403867
303	Ubiquitination	SSCRNYNKQASEQNW HHCCCCCHHHHHCHH	36.56	21890473
306	Phosphorylation	RNYNKQASEQNWANY CCCCHHHHHCHHHHH	36.90	26503892
313	Phosphorylation	SEQNWANYSAEQNRM HHCHHHHHHHHHHCC	11.08	21945579
314	Phosphorylation	EQNWANYSAEQNRMG HCHHHHHHHHHHCCC	25.74	19664994
325	Phosphorylation	NRMGQAGSTISNSHA HCCCCCCCCCCCCCC	26.11	26503892
326	Phosphorylation	RMGQAGSTISNSHAQ CCCCCCCCCCCCCCC	27.75	30266825
328	Phosphorylation	GQAGSTISNSHAQPF CCCCCCCCCCCCCCC	32.16	26503892
330	Phosphorylation	AGSTISNSHAQPFDF CCCCCCCCCCCCCCC	17.26	30266825
344	Phosphorylation	FPDDNQNSKKLAAGH CCCCCCCCCCCCCCC	22.77	23403867
345	Ubiquitination	PDDNQNSKKLAAGHE CCCCCCCCCCCCCCC	60.39	-
346	Ubiquitination	DDNQNSKKLAAGHEL CCCCCCCCCCCCCCC	43.08	-
364	Phosphorylation	AIVDQRPSSRASSRA EEECCCCCCCHHHCC	34.35	26503892
365	Phosphorylation	IVDQRPSSRASSRAS EECCCCCCCHHHCCC	34.25	26503892
368	Phosphorylation	QRPSSRASSRASSRP CCCCCCHHHCCCCCC	21.17	26503892
369	Phosphorylation	RPSSRASSRASSRPR CCCCCHHHCCCCCCC	30.77	26503892
372	Phosphorylation	SRASSRASSRPRPDD CCHHHCCCCCCCCCC	26.27	30266825
373	Phosphorylation	RASSRASSRPRPDDL CHHHCCCCCCCCCCC	45.37	30266825

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
247	Y	Phosphorylation	Kinase	SRC	P12931	PSP
255	S	Phosphorylation	Kinase	CDK1	P06493	PSP
255	S	Phosphorylation	Kinase	MAPKAPK2	P49137	PSP
262	S	Phosphorylation	Kinase	CDK1	P06493	PSP
265	Y	Phosphorylation	Kinase	SRC	Q9WUD9	PSP
265	Y	Phosphorylation	Kinase	SRC	P12931	PSP
279	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
279	S	Phosphorylation	Kinase	MAPKAPK2	P49137	PSP
282	S	Phosphorylation	Kinase	MAPKAPK2	P49137	PSP
282	S	Phosphorylation	Kinase	MAPK14	Q16539	GPS
313	Y	Phosphorylation	Kinase	SRC	P12931	PSP
325	S	Phosphorylation	Kinase	CK1	-	Uniprot
325	S	Phosphorylation	Kinase	CK1-FAMILY	-	GPS
325	S	Phosphorylation	Kinase	CK1A	P48729	PSP
328	S	Phosphorylation	Kinase	CK1	-	Uniprot
328	S	Phosphorylation	Kinase	CK1A	P48729	PSP
328	S	Phosphorylation	Kinase	CK1-FAMILY	-	GPS
330	S	Phosphorylation	Kinase	CK1	-	Uniprot
330	S	Phosphorylation	Kinase	CK1-FAMILY	-	GPS
330	S	Phosphorylation	Kinase	CK1A	P48729	PSP
364	S	Phosphorylation	Kinase	PKACA	P17612	PSP
365	S	Phosphorylation	Kinase	PKACA	P17612	PSP
368	S	Phosphorylation	Kinase	PRKCG	P05129	Uniprot
368	S	Phosphorylation	Kinase	PRKCE	Q02156	GPS
368	S	Phosphorylation	Kinase	PRKCD	Q05655	Uniprot
368	S	Phosphorylation	Kinase	PKCA	P17252	PSP
369	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
372	S	Phosphorylation	Kinase	PKCA	P17252	PSP
373	S	Phosphorylation	Kinase	AKT1	P31749	PSP
373	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	NEDD4	P46934	PMID:19835873

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
271	C	S-nitrosylation	-
S-nitrosylation at Cys-271 is enriched at the muscle endothelial gap junction in arteries, it augments channel permeability and may regulate of smooth muscle cell to endothelial cell communication.
325	S	Phosphorylation	12270943
Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly.
328	S	Phosphorylation	12270943
Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly.
330	S	Phosphorylation	12270943
Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly.
368	S	Phosphorylation	12270943
Phosphorylated at Ser-368 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of gap junction activity (By similarity).
368	S	Phosphorylation	12270943
Phosphorylation at Ser-368 by PRKCD triggers its internalization into small vesicles leading to proteasome-mediated degradation (By similarity).

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 CXA1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MK07_HUMAN	MAPK7	physical	12637502
CXA1_HUMAN	GJA1	physical	11739633
CXA3_HUMAN	GJA3	physical	11739633
CXA5_HUMAN	GJA5	physical	11557558
KC1D_HUMAN	CSNK1D	physical	12270943
ZO1_HUMAN	TJP1	physical	9707407
KPCE_HUMAN	PRKCE	physical	10679481
CAV1_HUMAN	CAV1	physical	11980479
NEDD4_HUMAN	NEDD4	physical	19907029
HGS_HUMAN	HGS	physical	19808888
TS101_HUMAN	TSG101	physical	19808888
EPS15_HUMAN	EPS15	physical	21554242
NEDD4_HUMAN	NEDD4	physical	19835873
UBQL4_HUMAN	UBQLN4	physical	20940304
UBQL4_HUMAN	UBQLN4	physical	18079109
UBQL4_HUMAN	UBQLN4	physical	24256120
PSMD2_HUMAN	PSMD2	physical	24256120
EPS15_HUMAN	EPS15	physical	25070368
STABP_HUMAN	STAMBP	physical	25070368
STXB2_HUMAN	STXBP2	physical	26186194
NDUA7_HUMAN	NDUFA7	physical	26186194
STXB1_HUMAN	STXBP1	physical	26186194
EF1A2_HUMAN	EEF1A2	physical	26186194
STXB1_HUMAN	STXBP1	physical	28514442
STXB2_HUMAN	STXBP2	physical	28514442
1433T_HUMAN	YWHAQ	physical	17008717
1433Z_HUMAN	YWHAZ	physical	17008717

Drug and Disease Associations

Kegg Disease
H00449	Oculodentodigital dysplasia
H00605	Deafness, autosomal recessive
H01095	Syndactyly
H01272	Hypoplastic left heart syndrome (HLHS)
OMIM Disease
164200	Oculodentodigital dysplasia (ODDD)
257850	Oculodentodigital dysplasia, autosomal recessive (ODDD-AR)
186100	Syndactyly 3 (SDTY3)
241550	Hypoplastic left heart syndrome 1 (HLHS1)
234100	Hallermann-Streiff syndrome (HSS)
600309	Atrioventricular septal defect 3 (AVSD3)
218400	Craniometaphyseal dysplasia, autosomal recessive (CMDR)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of CXA1_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Casein kinase 1 regulates connexin-43 gap junction assembly."; Cooper C.D., Lampe P.D.; J. Biol. Chem. 277:44962-44968(2002). Cited for: PHOSPHORYLATION AT SER-325; SER-328 AND SER-330 BY CSNK1D/CK1, ANDINTERACTION WITH CSNK1D.	12270943 [Abstract]
"Phosphorylation of serine 262 in the gap junction protein connexin-43regulates DNA synthesis in cell-cell contact forming cardiomyocytes."; Doble B.W., Dang X., Ping P., Fandrich R.R., Nickel B.E., Jin Y.,Cattini P.A., Kardami E.; J. Cell Sci. 117:507-514(2004). Cited for: PHOSPHORYLATION AT SER-262.	14702389 [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-247 AND TYR-313, ANDMASS SPECTROMETRY.	18083107 [Abstract]

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