AiPD: Autoinhibited Protein Database

P31321

Gene name	PRKAR1B
Protein name	cAMP-dependent protein kinase type I-beta regulatory subunit
Names
Species	Homo sapiens (Human)
KEGG Pathway	hsa:5575
EC number
Protein Class	CAMP-DEPENDENT PROTEIN KINASE REGULATORY CHAIN (PTHR11635)

Descriptions

PKA is a major intracellular receptor of cAMP and modulates diverse cellular signalings. The N-terminal regulatory domain contains a pseudosubstrate sequence that may interact with the catalytic kinase domain.

Autoinhibitory domains (AIDs)

Target domain	137-253 (Cyclic nucleotide-binding domain)
Relief mechanism	Ligand binding
Assay	Mutagenesis experiment

AID

97-101 (Autoinhibitory segment)

Target domain

137-253 (Cyclic nucleotide-binding domain)

Relief mechanism

Ligand binding (cAMP binding)

Assay

Mutagenesis experiment

Accessory elements

No accessory elements

References

Diskar M et al. (2007) "Molecular basis for isoform-specific autoregulation of protein kinase A", Cellular signalling, 19, 2024-34

Autoinhibited structure

Activated structure

3 structures for P31321

Entry ID	Method	Resolution	Chain	Position	Source
4DIN	X-ray	370 A	B	1-381	PDB
4F9K	X-ray	280 A	A/B/C/D	11-73	PDB
AF-P31321-F1	Predicted				AlphaFoldDB

288 variants for P31321

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA366537494 rs1278318079	2	A>S		No	ClinGen gnomAD
rs1201489213 CA366537478	3	S>F		No	ClinGen TOPMed
rs769267700 CA4110339	4	P>L		No	ClinGen ExAC TOPMed gnomAD
rs769267700 CA366537471	4	P>R		No	ClinGen ExAC TOPMed gnomAD
rs201102239 CA152342063	6	A>P		No	ClinGen Ensembl
CA366537450 rs201102239	6	A>S		No	ClinGen Ensembl
CA4110336 rs776389916	10	E>*		No	ClinGen ExAC gnomAD
rs770920851 CA4110335	10	E>G		No	ClinGen ExAC gnomAD
CA152342053 rs954428465	11	E>K		No	ClinGen TOPMed
rs1029957175 CA152342048	12	D>G		No	ClinGen Ensembl
CA366537346 rs1208723237	12	D>N		No	ClinGen TOPMed gnomAD
CA4110333 rs777626805	13	E>D		No	ClinGen ExAC gnomAD
CA366537307 rs1431535923	13	E>K		No	ClinGen gnomAD
rs1431535923 CA366537306	13	E>Q		No	ClinGen gnomAD
CA366537284 rs1287831986	14	S>G		No	ClinGen TOPMed
CA4110332 rs772059505	17	G>C		No	ClinGen ExAC TOPMed gnomAD
rs1457441061 CA366537180	18	C>Y		No	ClinGen gnomAD
CA4110330 rs780473276	22	V>L		No	ClinGen ExAC
CA366537026 rs1200873650	24	L>R		No	ClinGen TOPMed gnomAD
CA4110329 rs756232064	26	G>R		No	ClinGen ExAC gnomAD
CA366536866 rs1231657079	29	Q>R		No	ClinGen TOPMed gnomAD
rs781504988 CA4110327	31	L>V		No	ClinGen ExAC gnomAD
CA366536511 rs530392908	34	C>F		No	ClinGen ExAC TOPMed gnomAD
CA4110326 rs530392908	34	C>Y		No	ClinGen ExAC TOPMed gnomAD
CA4110325 rs751808123	35	I>M		No	ClinGen ExAC gnomAD
CA366536498 rs1448693349	35	I>T		No	ClinGen gnomAD
rs764518494 CA4110324	36	V>I		No	ClinGen ExAC TOPMed gnomAD
rs763352779 CA4110323	37	H>N		No	ClinGen ExAC gnomAD
rs752312422 CA4110322	39	C>W		No	ClinGen ExAC gnomAD
rs61732492 CA152342007	40	I>F		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
RCV000952534 CA4110321 rs61732492	40	I>V		No	ClinGen ClinVar 1000Genomes ESP ExAC TOPMed dbSNP gnomAD
CA4110320 rs780256262	41	S>F		No	ClinGen ExAC TOPMed gnomAD
rs1180688827 CA366536384	43	P>A		No	ClinGen TOPMed gnomAD
rs1180688827 CA366536383	43	P>S		No	ClinGen TOPMed gnomAD
CA366536365 rs1199257560	44	E>A		No	ClinGen gnomAD
CA366536360 rs1583452245	44	E>D		No	ClinGen Ensembl
rs770705531 CA4110318	44	E>K		No	ClinGen ExAC gnomAD
rs907917655 CA366536351	45	R>C		No	ClinGen TOPMed gnomAD
CA4110317 rs760656187	45	R>L		No	ClinGen ExAC TOPMed gnomAD
rs907917655 CA152341995	45	R>S		No	ClinGen TOPMed gnomAD
rs960120671 CA152341991	46	P>S		No	ClinGen TOPMed
rs1234344329 CA366536304	48	K>R		No	ClinGen gnomAD
RCV000416507 rs1057519490 CA16044247	50	L>R		No	ClinGen ClinVar Ensembl dbSNP
CA152341988 rs879938337	51	R>W		No	ClinGen TOPMed gnomAD
CA152341981 rs189408478	53	H>L		No	ClinGen 1000Genomes ExAC gnomAD
CA4110314 rs189408478	53	H>R		No	ClinGen 1000Genomes ExAC gnomAD
CA4110315 rs771971611	53	H>Y		No	ClinGen ExAC gnomAD
rs775816536 CA4110313	54	F>I		No	ClinGen ExAC TOPMed gnomAD
CA4110312 rs770164934	54	F>L		No	ClinGen ExAC TOPMed gnomAD
rs756143798 CA152341970	59	K>E		No	ClinGen Ensembl
rs374729888 CA152326888	61	E>D		No	ClinGen ESP gnomAD
rs1308812960 CA366533190	61	E>K		No	ClinGen gnomAD
rs371160585 CA4110252	62	N>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs947912556 CA152326882	63	R>K		No	ClinGen Ensembl
rs772109340 CA4110251	64	Q>K		No	ClinGen ExAC gnomAD
rs530700943 CA4110249	65	I>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1331695805 CA366533135	65	I>V		No	ClinGen gnomAD
CA366533112 rs1377826756	66	L>F		No	ClinGen TOPMed
rs183383238 CA4110248	67	A>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs140110814 CA4110245	68	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs370909605 CA4110246	68	R>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs150538055 CA366533061	70	K>N		No	ClinGen ESP gnomAD
rs1472463058 CA366533065	70	K>T		No	ClinGen gnomAD
rs1212455168 CA366533057	71	S>T		No	ClinGen TOPMed
rs201442077 CA4110241	72	N>I		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA366532770 rs1583409023	72	N>K		No	ClinGen Ensembl
CA4110242 rs201442077	72	N>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA4110240 rs777702342	73	S>P		No	ClinGen ExAC gnomAD
rs1053414449 CA152326837	74	Q>R		No	ClinGen TOPMed gnomAD
CA4110239 rs758284378	75	S>L		No	ClinGen ExAC TOPMed gnomAD
rs1379696670 CA366532749	75	S>P		No	ClinGen gnomAD
CA366532734 rs1286473445	76	D>E		No	ClinGen gnomAD
CA4110236 rs369017795	76	D>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs367822885 CA4110235	78	H>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA4110232 rs774298132	83	S>L		No	ClinGen ExAC TOPMed gnomAD
CA152326807 rs1018426691	84	P>A		No	ClinGen Ensembl
rs200749428 CA4110230	84	P>L		No	ClinGen ExAC TOPMed gnomAD
rs770020244 CA366532674	85	T>I		No	ClinGen ExAC TOPMed gnomAD
rs770020244 CA366532673	85	T>N		No	ClinGen ExAC TOPMed gnomAD
CA366532677 rs1583408915	85	T>P		No	ClinGen Ensembl
rs770020244 RCV000488004 CA4110228	85	T>S		No	ClinGen ClinVar ExAC TOPMed dbSNP gnomAD
CA4110226 rs199799634	87	P>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA4110225 rs770716715	87	P>L		No	ClinGen ExAC TOPMed gnomAD
CA152326782 rs770716715	87	P>R		No	ClinGen ExAC TOPMed gnomAD
CA152326790 rs199799634	87	P>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs199799634 CA152326794	87	P>T		No	ClinGen ESP ExAC TOPMed gnomAD
rs1583408853 CA366532662	88	N>T		No	ClinGen Ensembl
CA4110222 rs148427628	89	P>A		No	ClinGen ESP ExAC TOPMed gnomAD
rs1442645314 CA366532654	89	P>R		No	ClinGen TOPMed
rs1554302238 CA366532629	93	A>D		No	ClinGen Ensembl
CA366532631 rs1261543204	93	A>P		No	ClinGen TOPMed gnomAD
CA366532630 rs1261543204	93	A>S		No	ClinGen TOPMed gnomAD
CA4110220 rs762351800	94	R>C		No	ClinGen ExAC TOPMed gnomAD
rs778958450 CA4110219	94	R>H		No	ClinGen ExAC TOPMed gnomAD
CA4110218 rs372454246	95	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs144462255 CA4110217	95	R>H		No	ClinGen ESP ExAC TOPMed gnomAD
CA4110216 rs767658145	96	R>Q		No	ClinGen ExAC gnomAD
CA366532613 COSM1451885 rs1397568926	97	R>*	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
CA366532611 rs1363373128	97	R>Q		No	ClinGen gnomAD
CA4110215 rs757483222	99	G>S		No	ClinGen ExAC gnomAD
CA4110213 rs764074623	100	V>M		No	ClinGen ExAC gnomAD
CA366532578 rs1562611130	103	E>K		No	ClinGen Ensembl
CA366532571 rs1461961254	104	V>M		No	ClinGen gnomAD
CA366532561 rs1422815556	105	Y>C		No	ClinGen gnomAD
CA366532552 rs1168379229	106	T>I		No	ClinGen gnomAD
CA366532528 rs558009253	109	D>E		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA152326728 rs1044891046	110	A>G		No	ClinGen TOPMed gnomAD
CA366532522 rs1255328948	111	V>M		No	ClinGen gnomAD
CA366532505 rs1317893149	113	Y>S		No	ClinGen gnomAD
rs894999329 CA152326718	114	V>A		No	ClinGen TOPMed
rs1216190199 CA366532502	114	V>I		No	ClinGen TOPMed
rs771483360 CA4110207	115	R>K		No	ClinGen ExAC TOPMed gnomAD
CA4110206 rs746639938	116	K>N		No	ClinGen ExAC gnomAD
CA4110176 rs557752784	117	V>L		No	ClinGen 1000Genomes ExAC gnomAD
rs1258812714 CA366531989	118	I>L		No	ClinGen gnomAD
CA4110174 rs752924825	123	K>N		No	ClinGen ExAC
CA4110173 rs779132910	124	T>S		No	ClinGen ExAC gnomAD
CA4110171 rs754375671	126	T>I		No	ClinGen ExAC gnomAD
CA4110170 rs147210283	127	A>V		No	ClinGen ESP ExAC gnomAD
CA152325240 rs185641179	139	A>P		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
RCV000937715 CA4110161 rs185641179	139	A>S		No	ClinGen ClinVar 1000Genomes ExAC TOPMed dbSNP gnomAD
rs185641179 CA4110162 COSM1222015	139	A>T	large_intestine [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
rs781030551 CA4110159	143	D>E		No	ClinGen ExAC gnomAD
CA4110157 rs150349181	147	S>G		No	ClinGen ESP ExAC TOPMed gnomAD
rs779330577 CA4110156	147	S>I		No	ClinGen ExAC gnomAD
rs1376732415 CA366533373	149	I>T		No	ClinGen gnomAD
CA4110125 rs759019649	151	D>H		No	ClinGen ExAC gnomAD
rs1197990666 CA366533355	152	A>S		No	ClinGen gnomAD
rs776586095 CA4110124	155	P>A		No	ClinGen ExAC TOPMed gnomAD
rs1196442493 CA366533319	157	T>S		No	ClinGen gnomAD
CA366533315 rs1381378463	158	H>D		No	ClinGen TOPMed
rs772049509 CA366533299	160	A>S		No	ClinGen ExAC TOPMed gnomAD
CA4110120 rs772049509	160	A>T		No	ClinGen ExAC TOPMed gnomAD
CA366533296 rs1236717328	160	A>V		No	ClinGen gnomAD
rs1384905393 CA366533291	161	G>A		No	ClinGen TOPMed
CA152305056 rs748546239	163	T>A		No	ClinGen TOPMed
rs1440738344 CA366533269	165	I>V		No	ClinGen TOPMed gnomAD
CA366533256 rs1583293378	166	Q>H		No	ClinGen Ensembl
CA366533246 rs1390773357	168	G>R		No	ClinGen gnomAD
CA366532852 rs1474825667	170	E>A		No	ClinGen gnomAD
CA366532851 rs1474825667	170	E>G		No	ClinGen gnomAD
rs1486008794 CA366532815	175	Y>D		No	ClinGen gnomAD
rs548436328 CA152303879	177	V>A		No	ClinGen 1000Genomes
CA4110087 rs76714196	177	V>I		No	ClinGen ExAC TOPMed gnomAD
CA4110088 rs76714196	177	V>L		No	ClinGen ExAC TOPMed gnomAD
rs767584744 CA4110083	181	E>D		No	ClinGen ExAC gnomAD
CA152303877 rs966434334	182	V>G		No	ClinGen Ensembl
CA4110080 rs765438930	183	D>E		No	ClinGen ExAC TOPMed gnomAD
CA4110082 rs761625232	183	D>H		No	ClinGen ExAC TOPMed gnomAD
CA366532751 rs761625232	183	D>N		No	ClinGen ExAC TOPMed gnomAD
CA152303865 rs761625232	183	D>Y		No	ClinGen ExAC TOPMed gnomAD
rs369261319 CA4110039	186	V>L		No	ClinGen ESP ExAC gnomAD
CA4110038 rs369261319	186	V>L		No	ClinGen ESP ExAC gnomAD
rs1374209048 CA366529316	188	G>*		No	ClinGen TOPMed gnomAD
CA366529318 rs1374209048	188	G>R		No	ClinGen TOPMed gnomAD
CA152292817 rs919271958	189	E>K		No	ClinGen Ensembl
rs764693130 CA4110035	193	N>T		No	ClinGen ExAC gnomAD
CA366529262 rs1433163289	194	I>V		No	ClinGen gnomAD
rs79694108 CA152292798	195	S>I		No	ClinGen Ensembl
rs76344857 CA152292795	196	E>K		No	ClinGen Ensembl
CA366529204 rs1472857461	197	G>R		No	ClinGen TOPMed
CA366529138 rs1415229301	201	G>R		No	ClinGen TOPMed
CA366529028 rs1340953562	208	G>S		No	ClinGen TOPMed
rs1245620469 CA366528972	214	T>N		No	ClinGen TOPMed
rs754809896 CA4110023	217	A>G		No	ClinGen ExAC TOPMed gnomAD
rs781497728 CA4110021	219	T>M		No	ClinGen ExAC TOPMed gnomAD
CA366528872 rs1402708435	220	D>E		No	ClinGen gnomAD
rs764447261 CA4110018	223	L>V		No	ClinGen ExAC TOPMed gnomAD
CA366528767 rs1189087134	227	D>Y		No	ClinGen TOPMed
CA152292678 rs1035890353	228	R>Q		No	ClinGen TOPMed
CA152292680 rs949298930	228	R>W		No	ClinGen TOPMed gnomAD
rs763536702 CA4110017	229	D>N		No	ClinGen ExAC gnomAD
COSM1091149 CA4110016 rs200069843	232	R>Q	endometrium [Cosmic]	No	ClinGen cosmic curated 1000Genomes ExAC TOPMed gnomAD
CA366528692 rs1383315406	232	R>W		No	ClinGen TOPMed gnomAD
rs765662228 CA4110015	233	R>H		No	ClinGen ExAC gnomAD
CA4109987 rs774230749	244	K>N		No	ClinGen ExAC gnomAD
rs763122625 CA4109986	247	E>Q		No	ClinGen ExAC TOPMed gnomAD
CA4109985 rs748978313	248	E>K		No	ClinGen ExAC TOPMed gnomAD
rs1337457288 CA366549616	251	S>R		No	ClinGen gnomAD
rs1352802448 CA366549577	256	L>R		No	ClinGen gnomAD
CA366549574 rs1229349513	257	E>K		No	ClinGen gnomAD
COSM1313223 CA366549573 rs1229349513	257	E>Q	urinary_tract [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1227082232 CA366547640	258	S>F		No	ClinGen TOPMed
CA4109957 rs780449319	261	K>M		No	ClinGen ExAC gnomAD
CA366547565 rs1353455427	261	K>N		No	ClinGen gnomAD
rs1289462089 CA366547532	262	W>*		No	ClinGen gnomAD
CA366547501 rs1228480924	264	R>C		No	ClinGen gnomAD
CA4109956 rs369460111	264	R>H		No	ClinGen ExAC TOPMed gnomAD
CA152336894 rs1012168442	267	V>M		No	ClinGen gnomAD
rs1317364396 CA366547408 COSM3412223	270	A>V	central_nervous_system [Cosmic]	No	ClinGen cosmic curated gnomAD
CA4109950 rs762416557	274	V>I		No	ClinGen ExAC TOPMed gnomAD
rs1474938425 CA366547376	275	Q>R		No	ClinGen gnomAD
CA152336870 rs879244482	277	E>G		No	ClinGen Ensembl
rs1014983486 CA152336867	282	I>V		No	ClinGen TOPMed
CA366547321 rs1183860614	283	V>M		No	ClinGen gnomAD
CA4109944 rs150032469	287	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
CA366547288 rs1214106044	288	P>T		No	ClinGen gnomAD
CA366547277 rs1449037803	289	G>E		No	ClinGen gnomAD
CA366547264 rs1445954537	291	D>E		No	ClinGen TOPMed
rs774763564 CA4109940	291	D>H		No	ClinGen ExAC gnomAD
rs774763564 CA4109939	291	D>N		No	ClinGen ExAC gnomAD
rs768734444 CA4109938	292	F>L		No	ClinGen ExAC
CA4109937 rs749359796	292	F>S		No	ClinGen ExAC
rs1333583191 CA366547253	293	Y>F		No	ClinGen gnomAD
rs1290867506 CA366547242	294	I>M		No	ClinGen TOPMed gnomAD
rs780541738 CA4109935	295	I>T		No	ClinGen ExAC
rs1229740071 CA366547234	296	T>A		No	ClinGen gnomAD
rs139109556 CA4109934	296	T>M		No	ClinGen ESP ExAC
rs1049931201 CA152319943	298	G>S		No	ClinGen gnomAD
CA366536453 rs1468433405	299	T>I		No	ClinGen TOPMed
rs376485407 CA366536434	300	A>P		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA152319925 rs376485407	300	A>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs376485407 CA4109891	300	A>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs978367242 CA152319923	300	A>V		No	ClinGen TOPMed gnomAD
CA366536399 rs528224231	301	S>C		No	ClinGen 1000Genomes
rs528224231 CA152319913	301	S>F		No	ClinGen 1000Genomes
CA4109887 rs375954492	305	R>C		No	ClinGen ESP ExAC gnomAD
CA4109886 rs748743633	305	R>H		No	ClinGen ExAC TOPMed gnomAD
rs866622752 CA152319880	306	R>L		No	ClinGen TOPMed gnomAD
rs866622752 CA152319883	306	R>Q		No	ClinGen TOPMed gnomAD
rs1034557450 CA152319886	306	R>W		No	ClinGen Ensembl
CA366536264 rs1213553033	307	S>F		No	ClinGen TOPMed
rs1465287512 CA366536237	309	N>D		No	ClinGen gnomAD
CA4109885 rs545787093	309	N>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs545787093 CA366536227	309	N>T		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1208140933 CA366536199	310	E>*		No	ClinGen gnomAD
COSM1698316 CA366536173 rs1224349212	311	E>K	skin [Cosmic]	No	ClinGen cosmic curated TOPMed
rs148058026 CA4109882	313	V>M		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs868699190 CA152319868	314	E>*		No	ClinGen gnomAD
CA366536081 rs1225788639	315	V>G		No	ClinGen gnomAD
CA366536074 rs866388676	316	G>E		No	ClinGen TOPMed
CA152319863 rs866388676	316	G>V		No	ClinGen TOPMed
CA152319864 rs866884774	316	G>W		No	ClinGen Ensembl
CA4109881 rs373481607	317	R>C		No	ClinGen ESP ExAC TOPMed gnomAD
rs750438730 CA4109880	317	R>H		No	ClinGen ExAC TOPMed gnomAD
CA4109878 rs757120955	320	P>H		No	ClinGen ExAC gnomAD
CA366536019 rs757120955	320	P>L		No	ClinGen ExAC gnomAD
CA4109879 rs575743523	320	P>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1425881007 CA366536009	321	S>P		No	ClinGen TOPMed
rs932720069 CA152319851	322	D>N		No	ClinGen TOPMed
rs1583182942 CA366535756	328	A>P		No	ClinGen Ensembl
rs1257531812 CA366535735	332	N>D		No	ClinGen TOPMed
rs1583182913 CA366535733	332	N>T		No	ClinGen Ensembl
CA4109841 rs77270969	333	R>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA4109840 rs77270969	333	R>Q		No	ClinGen ESP ExAC TOPMed gnomAD
rs1158275868 CA366535727	333	R>W		No	ClinGen gnomAD
rs1414244710 CA366535725	334	P>S		No	ClinGen gnomAD
CA4109838 rs758240013	335	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA366535718 rs1475000361	335	R>W		No	ClinGen gnomAD
CA4109837 rs754010354	336	A>V		No	ClinGen ExAC gnomAD
rs374626599 CA4109833	339	V>I		No	ClinGen ESP ExAC TOPMed gnomAD
rs370144226 CA4109831	340	V>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs370144226 CA4109830	340	V>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs763428499 CA366535683	342	R>G		No	ClinGen ExAC TOPMed gnomAD
CA152319165 rs922802389	342	R>P		No	ClinGen TOPMed gnomAD
CA366535682 rs922802389	342	R>Q		No	ClinGen TOPMed gnomAD
rs763428499 CA4109829	342	R>W		No	ClinGen ExAC TOPMed gnomAD
CA152319164 rs1039837379	343	G>E		No	ClinGen TOPMed gnomAD
CA152319161 rs749969779	344	P>L		No	ClinGen Ensembl
CA366535640 rs1159982055	346	K>R		No	ClinGen gnomAD
CA366535622 rs1217754758	347	C>W		No	ClinGen TOPMed
rs13230810 CA152319142	351	D>N		No	ClinGen gnomAD
rs577305117 CA152319136	351	D>V		No	ClinGen 1000Genomes
CA366535581 rs13230810	351	D>Y		No	ClinGen gnomAD
CA366535568 rs1050898374	352	R>L		No	ClinGen gnomAD
CA366535570 rs1050898374	352	R>P		No	ClinGen gnomAD
rs1050898374 CA152319120	352	R>Q		No	ClinGen gnomAD
rs201388730 CA4109822	352	R>W		No	ClinGen ESP ExAC gnomAD
rs771814846 CA4109821	353	P>H		No	ClinGen ExAC gnomAD
rs747945652 CA4109820	354	R>C		No	ClinGen ExAC gnomAD
CA366535553 rs1208818929	354	R>H		No	ClinGen gnomAD
CA366535517 rs756349133	357	R>C		No	ClinGen ExAC gnomAD
CA4109818 rs756349133	357	R>G		No	ClinGen ExAC gnomAD
CA4109817 rs376573570	357	R>H		No	ClinGen ESP ExAC gnomAD
CA366535500 rs1159035224	358	V>G		No	ClinGen gnomAD
rs1432880742 CA366535485	360	G>E		No	ClinGen gnomAD
rs1192574620 CA366535480	361	P>S		No	ClinGen TOPMed
CA366535464 rs1377686546	363	S>C		No	ClinGen TOPMed
rs757327115 CA4109814	364	E>D		No	ClinGen ExAC gnomAD
CA366535438 rs1167223035	367	K>R		No	ClinGen gnomAD
rs1406171271 CA366535423	369	N>S		No	ClinGen gnomAD
CA4109811 rs758769513	371	Q>E		No	ClinGen ExAC gnomAD
rs753124715 CA4109810	371	Q>R		No	ClinGen ExAC gnomAD
rs765576596 CA4109809	372	R>C		No	ClinGen ExAC gnomAD
rs759197351 CA4109808	372	R>H		No	ClinGen ExAC gnomAD
rs776198627 CA366535394	374	N>D		No	ClinGen ExAC TOPMed gnomAD
rs776198627 CA4109807	374	N>H		No	ClinGen ExAC TOPMed gnomAD
CA4109806 rs765864817	378	S>F		No	ClinGen ExAC

1 associated diseases with P31321

[MIM: 619680]: Marbach-Schaaf neurodevelopmental syndrome (MASNS)

An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, speech delay, behavioral abnormalities, hypotonia, and movement disorders including dyspraxia, apraxia, and clumsiness. More variable features include high pain tolerance, sleep disturbances, and variable non-specific dysmorphic features. {ECO:0000269|PubMed:33833410}. Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID

An autosomal dominant neurodevelopmental disorder characterized by global developmental delay, speech delay, behavioral abnormalities, hypotonia, and movement disorders including dyspraxia, apraxia, and clumsiness. More variable features include high pain tolerance, sleep disturbances, and variable non-specific dysmorphic features. {ECO:0000269|PubMed:33833410}. Note=The disease is caused by variants affecting the gene represented in this entry.

8 regional properties for P31321

Type	Name	Position	InterPro Accession
domain	Cyclic nucleotide-binding domain	137 - 253	IPR000595-1
domain	Cyclic nucleotide-binding domain	255 - 376	IPR000595-2
domain	cAMP-dependent protein kinase regulatory subunit, dimerization-anchoring domain	25 - 62	IPR003117
conserved_site	Cyclic nucleotide-binding, conserved site	164 - 180	IPR018488-1
conserved_site	Cyclic nucleotide-binding, conserved site	200 - 217	IPR018488-2
conserved_site	Cyclic nucleotide-binding, conserved site	282 - 298	IPR018488-3
conserved_site	Cyclic nucleotide-binding, conserved site	324 - 341	IPR018488-4
domain	RIbeta, dimerization/docking domain	11 - 64	IPR042818

Functions

		Description
EC Number
Subcellular Localization	Cell membrane
PANTHER Family	PTHR11635	CAMP-DEPENDENT PROTEIN KINASE REGULATORY CHAIN
PANTHER Subfamily	PTHR11635:SF126	CAMP-DEPENDENT PROTEIN KINASE TYPE I-BETA REGULATORY SUBUNIT
PANTHER Protein Class	kinase modulator
PANTHER Pathway Category	Gonadotropin-releasing hormone receptor pathway PKA Metabotropic glutamate receptor group III pathway PKA Muscarinic acetylcholine receptor 2 and 4 signaling pathway PKA GABA-B receptor II signaling PKA Transcription regulation by bZIP transcription factor PKA Metabotropic glutamate receptor group II pathway PKA Heterotrimeric G-protein signaling pathway-Gi alpha and Gs alpha mediated pathway PKA-r Hedgehog signaling pathway PKA Endothelin signaling pathway PKA Metabotropic glutamate receptor group I pathway PKA

9 GO annotations of cellular component

Name	Definition
cAMP-dependent protein kinase complex	An enzyme complex, composed of regulatory and catalytic subunits, that catalyzes protein phosphorylation. Inactive forms of the enzyme have two regulatory chains and two catalytic chains; activation by cAMP produces two active catalytic monomers and a regulatory dimer.
ciliary base	Area of the cilium (also called flagellum) where the basal body and the axoneme are anchored to the plasma membrane. The ciliary base encompasses the distal part of the basal body, transition fibers and transition zone and is structurally and functionally very distinct from the rest of the cilium. In this area proteins are sorted and filtered before entering the cilium, and many ciliary proteins localize specifically to this area.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
glutamatergic synapse	A synapse that uses glutamate as a neurotransmitter.
hippocampal mossy fiber to CA3 synapse	One of the giant synapses that form between the mossy fiber axons of dentate gyrus granule cells and the large complex spines of CA3 pyramidal cells. It consists of a giant bouton known as the mossy fiber expansion, synapsed to the complex, multiheaded spine (thorny excresence) of a CA3 pyramidal cell.
multivesicular body	A type of endosome in which regions of the limiting endosomal membrane invaginate to form internal vesicles; membrane proteins that enter the internal vesicles are sequestered from the cytoplasm.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
Schaffer collateral - CA1 synapse	A synapse between the Schaffer collateral axon of a CA3 pyramidal cell and a CA1 pyramidal cell.

4 GO annotations of molecular function

Name	Definition
cAMP binding	Binding to cAMP, the nucleotide cyclic AMP (adenosine 3',5'-cyclophosphate).
cAMP-dependent protein kinase inhibitor activity	Binds to and stops, prevents or reduces the activity of a cAMP-dependent protein kinase.
cAMP-dependent protein kinase regulator activity	Modulation of the activity of the enzyme cAMP-dependent protein kinase.
protein kinase A catalytic subunit binding	Binding to one or both of the catalytic subunits of protein kinase A.

5 GO annotations of biological process

Name	Definition
learning or memory	The acquisition and processing of information and/or the storage and retrieval of this information over time.
modulation of chemical synaptic transmission	Any process that modulates the frequency or amplitude of synaptic transmission, the process of communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. Amplitude, in this case, refers to the change in postsynaptic membrane potential due to a single instance of synaptic transmission.
negative regulation of cAMP-dependent protein kinase activity	Any process that stops, prevents or reduces the frequency, rate or extent of cAMP-dependent protein kinase activity.
protein phosphorylation	The process of introducing a phosphate group on to a protein.
regulation of synaptic vesicle cycle	Any process that modulates the frequency, rate or extent of the synaptic vesicle cycle.

22 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P31322	PRKAR2B	cAMP-dependent protein kinase type II-beta regulatory subunit	Bos taurus (Bovine)	EV
P00514	PRKAR1A	cAMP-dependent protein kinase type I-alpha regulatory subunit	Bos taurus (Bovine)	EV
P00515	PRKAR2A	cAMP-dependent protein kinase type II-alpha regulatory subunit	Bos taurus (Bovine)	EV
Q5ZM91	PRKAR1A	cAMP-dependent protein kinase type I-alpha regulatory subunit	Gallus gallus (Chicken)	SS
P81900	Pka-R2	cAMP-dependent protein kinase type II regulatory subunit	Drosophila melanogaster (Fruit fly)	PR
P16905	Pka-R1	cAMP-dependent protein kinase type I regulatory subunit	Drosophila melanogaster (Fruit fly)	PR
Q96M20	CNBD2	Cyclic nucleotide-binding domain-containing protein 2	Homo sapiens (Human)	PR
P13861	PRKAR2A	cAMP-dependent protein kinase type II-alpha regulatory subunit	Homo sapiens (Human)	PR
P31323	PRKAR2B	cAMP-dependent protein kinase type II-beta regulatory subunit	Homo sapiens (Human)	PR
P10644	PRKAR1A	cAMP-dependent protein kinase type I-alpha regulatory subunit	Homo sapiens (Human)	EV
P12367	Prkar2a	cAMP-dependent protein kinase type II-alpha regulatory subunit	Mus musculus (Mouse)	PR
Q9D5U8	Cnbd2	Cyclic nucleotide-binding domain-containing protein 2	Mus musculus (Mouse)	PR
P31324	Prkar2b	cAMP-dependent protein kinase type II-beta regulatory subunit	Mus musculus (Mouse)	PR
Q9DBC7	Prkar1a	cAMP-dependent protein kinase type I-alpha regulatory subunit [Cleaved into: cAMP-dependent protein kinase type I-alpha regulatory subunit, N-terminally processed]	Mus musculus (Mouse)	SS
P12849	Prkar1b	cAMP-dependent protein kinase type I-beta regulatory subunit	Mus musculus (Mouse)	PR
P05207	PRKAR2A	cAMP-dependent protein kinase type II-alpha regulatory subunit	Sus scrofa (Pig)	SS
P07802	PRKAR1A	cAMP-dependent protein kinase type I-alpha regulatory subunit	Sus scrofa (Pig)	SS
P09456	Prkar1a	cAMP-dependent protein kinase type I-alpha regulatory subunit	Rattus norvegicus (Rat)	SS
P12368	Prkar2a	cAMP-dependent protein kinase type II-alpha regulatory subunit	Rattus norvegicus (Rat)	PR
P12369	Prkar2b	cAMP-dependent protein kinase type II-beta regulatory subunit	Rattus norvegicus (Rat)	PR
P81377	Prkar1b	cAMP-dependent protein kinase type I-beta regulatory subunit	Rattus norvegicus (Rat)	PR
P30625	kin-2	cAMP-dependent protein kinase regulatory subunit	Caenorhabditis elegans	SS

10	20	30	40	50	60
MASPPACPSE	EDESLKGCEL	YVQLHGIQQV	LKDCIVHLCI	SKPERPMKFL	REHFEKLEKE
70	80	90	100	110	120
ENRQILARQK	SNSQSDSHDE	EVSPTPPNPV	VKARRRRGGV	SAEVYTEEDA	VSYVRKVIPK
130	140	150	160	170	180
DYKTMTALAK	AISKNVLFAH	LDDNERSDIF	DAMFPVTHIA	GETVIQQGNE	GDNFYVVDQG
190	200	210	220	230	240
EVDVYVNGEW	VTNISEGGSF	GELALIYGTP	RAATVKAKTD	LKLWGIDRDS	YRRILMGSTL
250	260	270	280	290	300
RKRKMYEEFL	SKVSILESLE	KWERLTVADA	LEPVQFEDGE	KIVVQGEPGD	DFYIITEGTA
310	320	330	340	350	360
SVLQRRSPNE	EYVEVGRLGP	SDYFGEIALL	LNRPRAATVV	ARGPLKCVKL	DRPRFERVLG
370	380
PCSEILKRNI	QRYNSFISLT	V