dbPTM

S4A4_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	S4A4_HUMAN
UniProt AC	Q9Y6R1
Protein Name	Electrogenic sodium bicarbonate cotransporter 1
Gene Name	SLC4A4
Organism	Homo sapiens (Human).
Sequence Length	1079
Subcellular Localization	Basolateral cell membrane Multi-pass membrane protein .
Protein Description	Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH.; Isoform 2: May have a higher activity than isoform 1..
Protein Sequence	MEDEAVLDRGASFLKHVCDEEEVEGHHTIYIGVHVPKSYRRRRRHKRKTGHKEKKEKERISENYSDKSDIENADESSSSILKPLISPAAERIRFILGEEDDSPAPPQLFTELDELLAVDGQEMEWKETARWIKFEEKVEQGGERWSKPHVATLSLHSLFELRTCMEKGSIMLDREASSLPQLVEMIVDHQIETGLLKPELKDKVTYTLLRKHRHQTKKSNLRSLADIGKTVSSASRMFTNPDNGSPAMTHRNLTSSSLNDISDKPEKDQLKNKFMKKLPRDAEASNVLVGEVDFLDTPFIAFVRLQQAVMLGALTEVPVPTRFLFILLGPKGKAKSYHEIGRAIATLMSDEVFHDIAYKAKDRHDLIAGIDEFLDEVIVLPPGEWDPAIRIEPPKSLPSSDKRKNMYSGGENVQMNGDTPHDGGHGGGGHGDCEELQRTGRFCGGLIKDIKRKAPFFASDFYDALNIQALSAILFIYLATVTNAITFGGLLGDATDNMQGVLESFLGTAVSGAIFCLFAGQPLTILSSTGPVLVFERLLFNFSKDNNFDYLEFRLWIGLWSAFLCLILVATDASFLVQYFTRFTEEGFSSLISFIFIYDAFKKMIKLADYYPINSNFKVGYNTLFSCTCVPPDPANISISNDTTLAPEYLPTMSSTDMYHNTTFDWAFLSKKECSKYGGNLVGNNCNFVPDITLMSFILFLGTYTSSMALKKFKTSPYFPTTARKLISDFAIILSILIFCVIDALVGVDTPKLIVPSEFKPTSPNRGWFVPPFGENPWWVCLAAAIPALLVTILIFMDQQITAVIVNRKEHKLKKGAGYHLDLFWVAILMVICSLMALPWYVAATVISIAHIDSLKMETETSAPGEQPKFLGVREQRVTGTLVFILTGLSVFMAPILKFIPMPVLYGVFLYMGVASLNGVQFMDRLKLLLMPLKHQPDFIYLRHVPLRRVHLFTFLQVLCLALLWILKSTVAAIIFPVMILALVAVRKGMDYLFSQHDLSFLDDVIPEKDKKKKEDEKKKKKKKGSLDSDNDDSDCPYSEKVPSIKIPMDIMEQQPFLSDSKPSDRERSPTFLERHTSC

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2 (in isoform 2)	Phosphorylation	-	75.71	30108239
2 (in isoform 3)	Phosphorylation	-	75.71	30108239
3 (in isoform 3)	Phosphorylation	-	62.10	30108239
3 (in isoform 2)	Phosphorylation	-	62.10	30108239
11 (in isoform 2)	Phosphorylation	-	9.67	25404012
11 (in isoform 3)	Phosphorylation	-	9.67	25404012
12	Phosphorylation	AVLDRGASFLKHVCD HHHHHHHHHHHHHCC	33.66	24670416
28	Phosphorylation	EEVEGHHTIYIGVHV HHHCCCEEEEEEEEC	15.14	-
30	Phosphorylation	VEGHHTIYIGVHVPK HCCCEEEEEEEECCH	7.87	22817900
38	Phosphorylation	IGVHVPKSYRRRRRH EEEECCHHHHHHHHH	20.15	26074081
39	Phosphorylation	GVHVPKSYRRRRRHK EEECCHHHHHHHHHH	17.79	26074081
49	Phosphorylation	RRRHKRKTGHKEKKE HHHHHCHHCCHHHHH	48.85	22817900
61	Phosphorylation	KKEKERISENYSDKS HHHHHHHCCCCCCHH	26.47	26074081
64	Phosphorylation	KERISENYSDKSDIE HHHHCCCCCCHHHHC	17.75	20363803
65	Phosphorylation	ERISENYSDKSDIEN HHHCCCCCCHHHHCC	50.58	22617229
68	Phosphorylation	SENYSDKSDIENADE CCCCCCHHHHCCCCC	49.13	22617229
76	Phosphorylation	DIENADESSSSILKP HHCCCCCCCCHHHHH	35.75	28464451
77	Phosphorylation	IENADESSSSILKPL HCCCCCCCCHHHHHH	26.51	28464451
78	Phosphorylation	ENADESSSSILKPLI CCCCCCCCHHHHHHH	30.58	28464451
79	Phosphorylation	NADESSSSILKPLIS CCCCCCCHHHHHHHC	33.61	28464451
86	Phosphorylation	SILKPLISPAAERIR HHHHHHHCCHHHHHH	19.03	28978645
163	Phosphorylation	HSLFELRTCMEKGSI HHHHHHHHHHHHCCE	28.91	19413330
167	Acetylation	ELRTCMEKGSIMLDR HHHHHHHHCCEEECC	30.95	11790169
206	Phosphorylation	ELKDKVTYTLLRKHR HHHHHHHHHHHHHHC	9.81	24719451
207	Phosphorylation	LKDKVTYTLLRKHRH HHHHHHHHHHHHHCH	15.22	19413330
219	Phosphorylation	HRHQTKKSNLRSLAD HCHHCCHHCHHHHHH	42.53	28857561
223 (in isoform 5)	Phosphorylation	-	30.95	27251275
223	Phosphorylation	TKKSNLRSLADIGKT CCHHCHHHHHHHCCC	30.95	28258704
229	Ubiquitination	RSLADIGKTVSSASR HHHHHHCCCHHHHHH	46.19	-
230	Phosphorylation	SLADIGKTVSSASRM HHHHHCCCHHHHHHH	22.02	28857561
232	Phosphorylation	ADIGKTVSSASRMFT HHHCCCHHHHHHHCC	25.97	25219547
233	Phosphorylation	DIGKTVSSASRMFTN HHCCCHHHHHHHCCC	26.40	25219547
235	Phosphorylation	GKTVSSASRMFTNPD CCCHHHHHHHCCCCC	26.65	25219547
239	Phosphorylation	SSASRMFTNPDNGSP HHHHHHCCCCCCCCC	36.18	25219547
245 (in isoform 5)	Phosphorylation	-	18.75	27251275
245	Phosphorylation	FTNPDNGSPAMTHRN CCCCCCCCCCCCCCC	18.75	22617229
249	Phosphorylation	DNGSPAMTHRNLTSS CCCCCCCCCCCCCCC	21.57	28122231
254 (in isoform 5)	Phosphorylation	-	30.06	27251275
254	Phosphorylation	AMTHRNLTSSSLNDI CCCCCCCCCCCCCCC	30.06	30266825
255	Phosphorylation	MTHRNLTSSSLNDIS CCCCCCCCCCCCCCC	22.54	30266825
255 (in isoform 5)	Phosphorylation	-	22.54	27251275
256	Phosphorylation	THRNLTSSSLNDISD CCCCCCCCCCCCCCC	33.34	23401153
256 (in isoform 5)	Phosphorylation	-	33.34	27251275
257	Phosphorylation	HRNLTSSSLNDISDK CCCCCCCCCCCCCCC	30.84	23401153
257 (in isoform 5)	Phosphorylation	-	30.84	27251275
262	Phosphorylation	SSSLNDISDKPEKDQ CCCCCCCCCCCCHHH	42.31	29255136
396	Phosphorylation	IRIEPPKSLPSSDKR CCCCCCCCCCCCCCC	51.81	24275569
399	Phosphorylation	EPPKSLPSSDKRKNM CCCCCCCCCCCCCCC	57.36	23403867
400	Phosphorylation	PPKSLPSSDKRKNMY CCCCCCCCCCCCCCC	45.25	23403867
407	Phosphorylation	SDKRKNMYSGGENVQ CCCCCCCCCCCCCCC	17.35	-
543	Phosphorylation	ERLLFNFSKDNNFDY EEHHHHCCCCCCCCH	39.96	28961369
641	N-linked_Glycosylation	PANISISNDTTLAPE CCCEECCCCCCCCCH	49.32	25568315
661	N-linked_Glycosylation	SSTDMYHNTTFDWAF CCCCCCCCCCCCEEE	24.27	25568315
675	Phosphorylation	FLSKKECSKYGGNLV EECHHHHHHHCCCCC	29.97	28857561
677	Phosphorylation	SKKECSKYGGNLVGN CHHHHHHHCCCCCCC	17.61	28857561
693	Phosphorylation	CNFVPDITLMSFILF CCCCCCHHHHHHHHH	24.64	28857561
696	Phosphorylation	VPDITLMSFILFLGT CCCHHHHHHHHHHHH	16.55	28857561
704	Phosphorylation	FILFLGTYTSSMALK HHHHHHHCCCHHHHH	11.65	30576142
705	Phosphorylation	ILFLGTYTSSMALKK HHHHHHCCCHHHHHH	17.73	30576142
706	Phosphorylation	LFLGTYTSSMALKKF HHHHHCCCHHHHHHH	14.01	30576142
715	Phosphorylation	MALKKFKTSPYFPTT HHHHHHCCCCCCCHH	37.76	26074081
716	Phosphorylation	ALKKFKTSPYFPTTA HHHHHCCCCCCCHHH	20.42	26074081
718	Phosphorylation	KKFKTSPYFPTTARK HHHCCCCCCCHHHHH	23.20	26074081
854	Phosphorylation	ISIAHIDSLKMETET HHHHHHHHCCCCCCC	29.32	-
941	Phosphorylation	KHQPDFIYLRHVPLR CCCCCEEEEECCCHH	9.55	-
992	Phosphorylation	AVRKGMDYLFSQHDL HHHHCHHHHHHHHCH	10.76	29083192
995	Phosphorylation	KGMDYLFSQHDLSFL HCHHHHHHHHCHHHH	24.82	27251275
1000 (in isoform 5)	Phosphorylation	-	29.80	27251275
1000	Phosphorylation	LFSQHDLSFLDDVIP HHHHHCHHHHHHCCC	29.80	27251275
1026	Phosphorylation	KKKKKKGSLDSDNDD HHHHHCCCCCCCCCC	37.57	22617229
1029	Phosphorylation	KKKGSLDSDNDDSDC HHCCCCCCCCCCCCC	43.54	22617229
1034	Phosphorylation	LDSDNDDSDCPYSEK CCCCCCCCCCCCCCC	43.93	26657352
1038	Phosphorylation	NDDSDCPYSEKVPSI CCCCCCCCCCCCCCC	35.47	28857561
1039	Phosphorylation	DDSDCPYSEKVPSIK CCCCCCCCCCCCCCE	18.98	25072903
1044	Phosphorylation	PYSEKVPSIKIPMDI CCCCCCCCCEECCCH	39.23	26074081
1059	Phosphorylation	MEQQPFLSDSKPSDR HHCCCCCCCCCCCCC	39.97	26074081
1061	Phosphorylation	QQPFLSDSKPSDRER CCCCCCCCCCCCCCC	42.99	26074081
1064	Phosphorylation	FLSDSKPSDRERSPT CCCCCCCCCCCCCCC	53.70	26074081
1069	Phosphorylation	KPSDRERSPTFLERH CCCCCCCCCCHHHHH	24.44	29255136
1071	Phosphorylation	SDRERSPTFLERHTS CCCCCCCCHHHHHCC	41.94	24670416
1077	Phosphorylation	PTFLERHTSC----- CCHHHHHCCC-----	37.70	24670416
1078	Phosphorylation	TFLERHTSC------ CHHHHHCCC------	16.23	20736484

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
12	S	Phosphorylation	Kinase	TTK	P33981	PSP
49	T	Phosphorylation	Kinase	PKA	-	Uniprot
65	S	Phosphorylation	Kinase	STK39	Q9UEW8	GPS
1026	S	Phosphorylation	Kinase	PRKACA	P17612	GPS
1026	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
1026	S	Phosphorylation	Kinase	PKA	-	Uniprot
1026	S	Phosphorylation	Kinase	PKA_GROUP	-	PhosphoELM

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
1026	S	Phosphorylation		11744745
Phosphorylation of Ser-1026 by PKA increases the binding of CA2 and changes the Na(+):HCO3(-) stoichiometry of the transporter from 3:1 to 2:1.

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 S4A4_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference	Domain-Domain Interactions
Oops, there are no PPI records of S4A4_HUMAN !!

Drug and Disease Associations

Kegg Disease
H00429	Proximal renal tubular acidosis (RTA type 2)
OMIM Disease
604278	Renal tubular acidosis, proximal, with ocular abnormalities and mental retardation (pRTA-OA)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of S4A4_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Phosphorylation of Ser(982) in the sodium bicarbonate cotransporterkNBC1 shifts the HCO(3)(-):Na(+) stoichiometry from 3:1 to 2:1 inmurine proximal tubule cells."; Gross E., Hawkins K., Pushkin A., Sassani P., Dukkipati R.,Abuladze N., Hopfer U., Kurtz I.; J. Physiol. (Lond.) 537:659-665(2001). Cited for: REGULATION, MUTAGENESIS OF SER-1026, AND PHOSPHORYLATION AT SER-1026.	11744745 [Abstract]
"Phosphorylation-induced modulation of pNBC1 function: distinct rolesfor the amino- and carboxy-termini."; Gross E., Fedotoff O., Pushkin A., Abuladze N., Newman D., Kurtz I.; J. Physiol. (Lond.) 549:673-682(2003). Cited for: REGULATION, MUTAGENESIS OF THR-49 AND SER-1026, AND PHOSPHORYLATION ATTHR-49.	12730338 [Abstract]

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