AiPD: Autoinhibited Protein Database

P15336

Gene name	ATF2 (CREB2, CREBP1)
Protein name	Cyclic AMP-dependent transcription factor ATF-2
Names	cAMP-dependent transcription factor ATF-2, Activating transcription factor 2, Cyclic AMP-responsive element-binding protein 2, CREB-2, cAMP-responsive element-binding protein 2, HB16, cAMP response element-binding protein CRE-BP1
Species	Homo sapiens (Human)
KEGG Pathway	hsa:1386
EC number
Protein Class	CYCLIC-AMP RESPONSE ELEMENT BINDING PROTEIN (PTHR19304)

Descriptions

ATF-2 is a cellular basic region-leucine zipper (bZIP) transcription factor that can mediate diverse transcriptional responses, including activation by the adenovirus Ela protein. ATF-2 contains an activation domain, required for transcriptional activity, but in the absence of an appropriate inducer, full-length ATF-2 is transcriptionally inactive. The ATF-2 bZIP (residues 350-415) suppresses the ATF-2 and the related Ela activation domains but not acidic- and glutamine-rich activation domains. The ATF-2 bZIP and activation domain are engaged in an inhibitory intramolecular interaction and the inducers of ATF-2 disrupt this interaction to activate transcription.

Autoinhibitory domains (AIDs)

Target domain	1-109 (Activation domain)
Relief mechanism	Partner binding
Assay	Deletion assay, Mutagenesis experiment, Structural analysis

AID

350-415 (bZIP domain)

Target domain

1-109 (Activation domain)

Relief mechanism

Partner binding (Binding of inducers such as adenovirus E1a protein)

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

Accessory elements

No accessory elements

References

Li XY et al. (1996) "Intramolecular inhibition of activating transcription factor-2 function by its DNA-binding domain", Genes & development, 10, 517-27

Laughlin JD et al. (2012) "Structural mechanisms of allostery and autoinhibition in JNK family kinases", Structure (London, England : 1993), 20, 2174-84

Autoinhibited structure

Activated structure

6 structures for P15336

Entry ID	Method	Resolution	Chain	Position	Source
1BHI	NMR	-	A	19-56	PDB
1T2K	X-ray	300 A	D	354-414	PDB
4H36	X-ray	300 A	B	48-55	PDB
6ZQS	X-ray	195 A	B	83-102	PDB
6ZR5	X-ray	270 A	C/D	20-58	PDB
AF-P15336-F1	Predicted				AlphaFoldDB

263 variants for P15336

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs545438784 CA349694544	2	K>N		No	ClinGen 1000Genomes TOPMed
rs545438784 CA61209382	2	K>N		No	ClinGen 1000Genomes TOPMed
rs778817652 CA349694537	3	F>L		No	ClinGen ExAC TOPMed gnomAD
rs1318451118 CA349694529	4	K>N		No	ClinGen TOPMed
rs757163479 CA1975572	4	K>R		No	ClinGen ExAC TOPMed gnomAD
rs749185655 CA1975571	7	V>A		No	ClinGen ExAC gnomAD
COSM1471323 CA349694503 rs1444053690	8	N>I	prostate [Cosmic]	No	ClinGen cosmic curated gnomAD
rs777892687 CA1975570	11	R>T		No	ClinGen ExAC gnomAD
CA1975552 rs769761585	14	K>N		No	ClinGen ExAC TOPMed gnomAD
rs751221583 CA61208717	15	D>A		No	ClinGen Ensembl
rs1291506008 CA349694426	17	W>*		No	ClinGen gnomAD
rs1200713578 CA349694402	20	S>N		No	ClinGen gnomAD
CA1975550 rs780721889	22	D>Y		No	ClinGen ExAC gnomAD
CA1975548 COSM441532 rs751165068	26	L>V	breast [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1299485584 CA349694332	29	A>V		No	ClinGen gnomAD
rs1364497278 CA349694302	33	G>S		No	ClinGen gnomAD
rs750772233 CA1975545	34	Q>R		No	ClinGen ExAC gnomAD
rs1233791447 CA349694249	38	N>S		No	ClinGen TOPMed
rs768144040 CA1975532	47	H>L		No	ClinGen ExAC gnomAD
CA349694184 rs1439930943	47	H>Y		No	ClinGen gnomAD
CA349694129 rs1478172478	54	K>N		No	ClinGen gnomAD
CA61207829 rs997411163	57	P>A		No	ClinGen TOPMed gnomAD
rs1489555819 CA349694098	59	R>H		No	ClinGen gnomAD
rs1426117150 CA349694032	67	D>G		No	ClinGen gnomAD
rs1164266829 CA349693901	86	N>H		No	ClinGen TOPMed
rs761545814 CA1975515	86	N>T		No	ClinGen ExAC gnomAD
COSM1293129 CA1975513 rs151176500	89	A>V	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA61207560 rs867492606 COSM136288	91	P>L	skin [Cosmic]	No	ClinGen cosmic curated Ensembl
rs764217636 CA61207558	92	F>L		No	ClinGen Ensembl
rs1432624112 CA349693846	94	N>H		No	ClinGen TOPMed
rs148615771 CA61207557	94	N>S		No	ClinGen ESP gnomAD
CA1975510 rs771614896	96	F>L		No	ClinGen ExAC gnomAD
CA1975509 rs373393705	101	E>D		No	ClinGen ESP ExAC TOPMed gnomAD
CA349693771 rs1377952600	104	I>F		No	ClinGen TOPMed
rs1377952600 CA349693772	104	I>V		No	ClinGen TOPMed
rs1309642618 CA349693757	106	K>E		No	ClinGen gnomAD
CA349693732 rs1349902601	107	M>I		No	ClinGen gnomAD
CA1975484 rs771528645	108	P>T		No	ClinGen ExAC gnomAD
CA1975482 rs372122622	113	P>R		No	ClinGen ESP ExAC gnomAD
CA1975483 rs573660989	113	P>S		No	ClinGen ExAC TOPMed gnomAD
rs1457696113 CA349693693	114	L>V		No	ClinGen gnomAD
rs907046130 CA61207544	115	A>G		No	ClinGen gnomAD
CA1975481 rs770478797	117	P>H		No	ClinGen ExAC TOPMed gnomAD
rs1045527447 CA61207543	117	P>T		No	ClinGen Ensembl
CA1975480 rs749040701	118	I>V		No	ClinGen ExAC TOPMed gnomAD
rs1233439087 CA349693635	123	I>F		No	ClinGen TOPMed
CA1975478 rs777972058	123	I>T		No	ClinGen ExAC gnomAD
CA1975477 rs756596035	125	E>G		No	ClinGen ExAC gnomAD
CA61207542 rs775754118	126	P>L		No	ClinGen gnomAD
rs1346198795 CA349693614	126	P>S		No	ClinGen gnomAD
rs781772910 CA1975475	128	V>A		No	ClinGen ExAC gnomAD
CA61207540 rs971528091	133	H>Q		No	ClinGen TOPMed
CA1975474 rs755043014	134	Q>R		No	ClinGen ExAC gnomAD
CA349693557 rs1317149846	135	D>G		No	ClinGen gnomAD
rs915967579 CA349693560	135	D>H		No	ClinGen TOPMed gnomAD
CA61207539 rs915967579	135	D>Y		No	ClinGen TOPMed gnomAD
rs1445463111 CA349693527	139	P>L		No	ClinGen TOPMed
rs559363401 CA1975472	140	H>Q		No	ClinGen 1000Genomes ExAC gnomAD
rs1398209425 CA349693524	140	H>Y		No	ClinGen gnomAD
rs758517668 CA1975471	141	P>L		No	ClinGen ExAC gnomAD
rs1386380681 CA349693491	145	T>I		No	ClinGen TOPMed gnomAD
rs1386380681 CA349693489	145	T>S		No	ClinGen TOPMed gnomAD
rs1295586489 CA349693485	146	S>N		No	ClinGen gnomAD
CA349693475 rs1574412697	147	D>V		No	ClinGen Ensembl
rs1444909690 CA349693463	149	K>E		No	ClinGen TOPMed
rs991793157 CA61207245	155	Q>P		No	ClinGen TOPMed
rs867211471 CA61207244	156	T>S		No	ClinGen Ensembl
CA349693166 rs1559080666	158	Q>R		No	ClinGen Ensembl
rs762556660 CA1975442	159	P>R		No	ClinGen ExAC TOPMed gnomAD
rs1377522393 CA349693156	159	P>S		No	ClinGen TOPMed
CA349693143 rs1213427555	160	T>S		No	ClinGen gnomAD
rs146410799 CA1975441	163	I>V		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA349693090 rs1376654626	165	R>C		No	ClinGen gnomAD
CA1975440 rs377033573	165	R>H		No	ClinGen ESP ExAC gnomAD
rs1449652173 CA349693085	166	P>S		No	ClinGen gnomAD
CA1975437 rs769112754	168	S>L		No	ClinGen ExAC gnomAD
CA349693057 rs1418657199	170	Q>H		No	ClinGen gnomAD
rs1292422582 CA349693047	171	V>G		No	ClinGen gnomAD
CA1975434 rs556192060	172	P>S		No	ClinGen 1000Genomes ExAC gnomAD
CA349692986 rs1186985164	176	L>F		No	ClinGen gnomAD
rs1440800022 CA349692966	177	T>R		No	ClinGen gnomAD
rs376867963 CA1975428	181	S>P		No	ClinGen ESP ExAC TOPMed gnomAD
rs1182167606 CA349692851	184	I>V		No	ClinGen TOPMed
rs1033953174 CA61207243	186	Q>*		No	ClinGen Ensembl
rs751413115 CA349692795	188	A>S		No	ClinGen ExAC TOPMed gnomAD
rs751413115 CA1975427	188	A>T		No	ClinGen ExAC TOPMed gnomAD
CA1975425 rs762312647	193	T>A		No	ClinGen ExAC gnomAD
CA349692732 rs762312647	193	T>P		No	ClinGen ExAC gnomAD
CA61207241 rs750958087	205	N>I		No	ClinGen gnomAD
CA349692574 rs750958087	205	N>S		No	ClinGen gnomAD
rs761534267 CA1975422	208	I>M		No	ClinGen ExAC gnomAD
CA61207240 rs537966016	208	I>V		No	ClinGen 1000Genomes TOPMed gnomAD
CA349692515 rs1328824308	210	P>S		No	ClinGen TOPMed
CA349692504 rs1427077296	212	P>A		No	ClinGen gnomAD
CA349692489 rs1231754089	214	P>R		No	ClinGen TOPMed
CA349692491 rs1574403645	214	P>S		No	ClinGen Ensembl
rs200549535 CA1975390	223	N>Y		No	ClinGen 1000Genomes ExAC gnomAD
rs770962595 CA1975389	228	P>S		No	ClinGen ExAC TOPMed gnomAD
CA349692374 rs1366462837	232	P>A		No	ClinGen gnomAD
CA1975388 rs376924681	232	P>R		No	ClinGen ESP ExAC TOPMed gnomAD
CA349692373 rs1366462837	232	P>S		No	ClinGen gnomAD
CA349692368 rs1438315912	233	A>E		No	ClinGen TOPMed gnomAD
CA349692367 rs1438315912	233	A>G		No	ClinGen TOPMed gnomAD
CA61207182 rs867049575	233	A>T		No	ClinGen Ensembl
rs773250879 CA1975387	235	I>V		No	ClinGen ExAC gnomAD
CA349692327 rs1463949371	239	N>K		No	ClinGen TOPMed gnomAD
rs1330624326 CA349692329	239	N>S		No	ClinGen TOPMed gnomAD
rs770045341 CA1975386	240	V>A		No	ClinGen ExAC gnomAD
rs1428555754 CA349692325	240	V>M		No	ClinGen gnomAD
CA1975384 rs779874682	242	V>F		No	ClinGen ExAC gnomAD
rs745760497 CA1975382	245	A>V		No	ClinGen ExAC gnomAD
CA1975381 rs778993699	246	V>D		No	ClinGen ExAC TOPMed gnomAD
rs1455881018 CA349692289	246	V>L		No	ClinGen gnomAD
CA61206959 rs369511491	248	L>H		No	ClinGen ESP TOPMed
rs762044358 CA1975368	249	V>I		No	ClinGen ExAC gnomAD
rs776749135 CA1975367	250	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs200331162 CA349691811	251	P>L		No	ClinGen gnomAD
rs200331162 CA61206957	251	P>Q		No	ClinGen gnomAD
CA61206956 rs891348913	252	V>I		No	ClinGen TOPMed gnomAD
rs1318700807 CA349691789	255	V>L		No	ClinGen gnomAD
rs778905720 CA1975364	259	P>A		No	ClinGen ExAC gnomAD
rs778905720 CA349691764	259	P>S		No	ClinGen ExAC gnomAD
CA1975363 rs770984722	260	G>E		No	ClinGen ExAC TOPMed gnomAD
rs1203020915 CA349691747	262	P>T		No	ClinGen TOPMed
CA349691737 rs1416926736	263	G>D		No	ClinGen gnomAD
CA349691715 rs1477879917 COSM1009807	267	P>S	endometrium [Cosmic]	No	ClinGen cosmic curated TOPMed
rs752358963 CA1975360	268	Q>H		No	ClinGen ExAC TOPMed gnomAD
rs780832335 CA1975358	269	P>L		No	ClinGen ExAC gnomAD
CA1975357 rs755278805	270	V>L		No	ClinGen ExAC gnomAD
CA1975356 rs751909387	271	Q>*		No	ClinGen ExAC gnomAD
CA349691569 rs1457897019	286	H>L		No	ClinGen gnomAD
rs749202587 CA1975342	286	H>Y		No	ClinGen ExAC gnomAD
rs1367218807 CA349691563	287	P>R		No	ClinGen gnomAD
CA1975341 rs570902505	288	P>A		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs570902505 CA1975340	288	P>S		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs900762834 CA61205369	289	V>L		No	ClinGen Ensembl
rs1422224831 CA349691541	291	N>S		No	ClinGen gnomAD
CA349691535 rs1191084388	292	G>S		No	ClinGen gnomAD
rs976905215 CA61205368	294	T>S		No	ClinGen TOPMed gnomAD
rs1262246460 CA349691513	295	V>G		No	ClinGen TOPMed gnomAD
rs1270693375 CA349691499	297	G>V		No	ClinGen TOPMed
rs546336948 CA1975338	298	H>R		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs796673103 CA61205367	300	S>N		No	ClinGen TOPMed gnomAD
CA1975337 rs372528750	300	S>R		No	ClinGen ESP ExAC gnomAD
CA1975336 rs146391410	301	G>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs1328414460 CA349691466	303	V>I		No	ClinGen gnomAD
CA61205365 rs139861769	305	T>I		No	ClinGen ESP TOPMed gnomAD
COSM1009806 rs141869874 CA1975332	311	R>*	endometrium [Cosmic]	No	ClinGen cosmic curated ESP ExAC gnomAD
rs141869874 CA1975331	311	R>G		No	ClinGen ESP ExAC gnomAD
rs371448160 CA349691412	311	R>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs371448160 CA1975330	311	R>Q		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs767222965 CA61205364 COSM1401403	312	P>L	kidney large_intestine [Cosmic]	No	ClinGen cosmic curated TOPMed gnomAD
rs766237973 CA1975326	313	Q>P		No	ClinGen ExAC gnomAD
rs1574355107 CA349691381	316	Q>H		No	ClinGen Ensembl
CA1975324 rs773144879	316	Q>K		No	ClinGen ExAC gnomAD
CA349691377 rs1431255656	317	Q>K		No	ClinGen gnomAD
CA61205363 rs934771554	318	P>S		No	ClinGen TOPMed
rs1429795394 CA349691363	319	A>D		No	ClinGen gnomAD
CA349691358 rs1559062591	320	T>K		No	ClinGen Ensembl
CA61205362 rs1006688344	320	T>P		No	ClinGen Ensembl
rs759250737 CA1975321	322	T>A		No	ClinGen ExAC
rs1574354995 CA349691328	325	T>S		No	ClinGen Ensembl
CA1975319 rs56300825	326	P>L		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs768206343 CA1975320	326	P>S		No	ClinGen ExAC gnomAD
rs768085622 CA1975303	331	H>R		No	ClinGen ExAC gnomAD
CA1975304 rs778902330	331	H>Y		No	ClinGen ExAC TOPMed gnomAD
rs746533020 CA1975302	333	T>A		No	ClinGen ExAC gnomAD
CA349691268 rs1391069828	333	T>I		No	ClinGen TOPMed
CA1975301 rs372839325 COSM476240	334	P>A	kidney [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA1975298 rs779123407	338	S>G		No	ClinGen ExAC TOPMed gnomAD
CA249194 rs138225471 RCV000202990	338	S>N		No	ClinGen ClinVar ESP ExAC TOPMed dbSNP gnomAD
CA349691240 rs779123407	338	S>R		No	ClinGen ExAC TOPMed gnomAD
rs200342330 CA61204916	341	G>S		No	ClinGen Ensembl
rs1225743969 CA349691213	342	R>C		No	ClinGen TOPMed gnomAD
rs1470433850 CA349691212	342	R>H		No	ClinGen gnomAD
CA1975296 rs778431198	343	R>P		No	ClinGen ExAC gnomAD
CA349691206 rs778431198	343	R>Q		No	ClinGen ExAC gnomAD
CA349691198 rs756205559	345	R>G		No	ClinGen ExAC TOPMed gnomAD
rs543271551 CA61204915	346	A>T		No	ClinGen gnomAD
rs781403920 CA1975293	349	E>K		No	ClinGen ExAC gnomAD
CA349691151 rs1374929488	352	D>N		No	ClinGen gnomAD
rs17223647 CA349691071 RCV000523073	362	N>K		No	ClinGen ClinVar Ensembl dbSNP
rs751860790 CA1975291	364	A>G		No	ClinGen ExAC gnomAD
CA349691058 rs751860790	364	A>V		No	ClinGen ExAC gnomAD
rs990847052 CA61204912	386	D>G		No	ClinGen TOPMed
rs912332500 CA61204910	392	G>S		No	ClinGen Ensembl
rs1305445815 CA349690826	396	S>G		No	ClinGen gnomAD
rs759092639 CA1975263	396	S>N		No	ClinGen ExAC TOPMed gnomAD
rs146453204 CA1975262	396	S>R		No	ClinGen ESP ExAC gnomAD
CA349690789 rs1240446063	402	R>K		No	ClinGen TOPMed gnomAD
rs1366657017 CA349690761	406	A>T		No	ClinGen TOPMed gnomAD
rs1371621433 CA349690709	414	A>P		No	ClinGen gnomAD
CA349690708 rs1371621433	414	A>S		No	ClinGen gnomAD
CA349690659 rs1239249727	421	T>A		No	ClinGen TOPMed
rs770334773 CA1975258	422	A>T		No	ClinGen ExAC TOPMed gnomAD
rs1172825782 CA349690647	423	M>L		No	ClinGen gnomAD
rs748557441 CA1975257	426	K>Q		No	ClinGen ExAC TOPMed gnomAD
CA1975256 rs777228973	428	G>S		No	ClinGen ExAC TOPMed gnomAD
rs1172153618 CA349690607	428	G>V		No	ClinGen gnomAD
rs1178754870 CA349690601	429	Y>C		No	ClinGen TOPMed
CA349690605 rs1338363259	429	Y>H		No	ClinGen gnomAD
rs747963598 CA1975229	431	T>I		No	ClinGen ExAC gnomAD
rs1195826928 CA349690555	434	K>R		No	ClinGen TOPMed
rs751503459 CA1975226	435	D>G		No	ClinGen ExAC gnomAD
rs1487016814 CA349690549	435	D>H		No	ClinGen gnomAD
rs765943326 CA1975225	436	D>G		No	ClinGen ExAC TOPMed gnomAD
rs142443599 CA1975224	438	S>T		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs1451201916 CA349690503	441	I>S		No	ClinGen TOPMed
CA1975222 rs764967442	442	S>T		No	ClinGen ExAC TOPMed gnomAD
rs777018630 CA1975220	444	P>L		No	ClinGen ExAC TOPMed gnomAD
CA349690488 rs1189633938	444	P>S		No	ClinGen gnomAD
rs1559040388 CA349690481	445	S>N		No	ClinGen Ensembl
CA349690452 rs1243071196	449	T>R		No	ClinGen gnomAD
CA1975218 rs761194042	452	I>V		No	ClinGen ExAC gnomAD
rs147478928 CA1975217 COSM1401400	456	S>L	large_intestine [Cosmic]	No	ClinGen cosmic curated ESP ExAC TOPMed gnomAD
CA349690401 rs147478928	456	S>W		No	ClinGen ESP ExAC TOPMed gnomAD
rs759627533 CA1975215	459	T>A		No	ClinGen ExAC gnomAD
rs555768175 CA1975214	461	N>S		No	ClinGen 1000Genomes ExAC gnomAD
rs771180346 CA1975213	462	G>E		No	ClinGen ExAC gnomAD
rs749514665 CA1975212	463	V>A		No	ClinGen ExAC TOPMed gnomAD
CA349690357 rs1235438300	464	S>G		No	ClinGen gnomAD
CA1975211 rs781022245	466	T>I		No	ClinGen ExAC TOPMed gnomAD
rs1574294221 CA349690343	466	T>P		No	ClinGen Ensembl
rs537479900 CA1975209	467	S>F		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1975210 rs768363052	467	S>P		No	ClinGen ExAC gnomAD
rs537479900 CA349690337	467	S>Y		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA1975208 rs771117385	468	K>N		No	ClinGen ExAC TOPMed gnomAD
CA349690316 rs954668428	470	E>D		No	ClinGen TOPMed gnomAD
CA349690309 rs1391734077	471	A>V		No	ClinGen gnomAD
CA1975207 rs749945884	472	V>I		No	ClinGen ExAC gnomAD
CA349690308 rs749945884	472	V>L		No	ClinGen ExAC gnomAD
CA1975206 rs749945884	472	V>L		No	ClinGen ExAC gnomAD
rs1461689318 CA349690295	474	T>N		No	ClinGen gnomAD
rs1255413728 CA349690278	477	L>F		No	ClinGen TOPMed
rs1262092548 CA349690255	480	M>I		No	ClinGen gnomAD
rs756908057 CA1975204	480	M>L		No	ClinGen ExAC gnomAD
CA349690257 rs1485313552	480	M>T		No	ClinGen TOPMed
COSM1528699 CA1975203 rs753454204	481	A>V	lung [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1417047179 CA349690234	483	Q>H		No	ClinGen TOPMed
rs760950559 CA1975201	483	Q>R		No	ClinGen ExAC gnomAD
rs1215611656 CA349690223	485	T>A		No	ClinGen gnomAD
CA61202960 rs900583670	486	E>D		No	ClinGen TOPMed gnomAD
rs1250999359 CA349690209	487	P>S		No	ClinGen gnomAD
rs1225453187 CA349690204	488	A>T		No	ClinGen gnomAD
rs753144395 CA1975200	491	Q>*		No	ClinGen ExAC TOPMed gnomAD
CA1975199 rs369362331	492	I>M		No	ClinGen ESP ExAC TOPMed gnomAD
rs749822996 CA61202959	492	I>V		No	ClinGen gnomAD
CA349690174 rs760104049	493	V>F		No	ClinGen ExAC gnomAD
CA1975198 COSM1733616 rs760104049	493	V>I	pancreas [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
rs1386879495 CA349690170	494	M>L		No	ClinGen TOPMed gnomAD
rs774384167 CA1975197	494	M>T		No	ClinGen ExAC gnomAD
rs1165802528 CA349690157	495	A>V		No	ClinGen gnomAD
CA1975196 rs770965410	497	S>F		No	ClinGen ExAC gnomAD
CA61202956 rs959081624	498	S>A		No	ClinGen Ensembl
rs201072854 CA61202955	500	S>P		No	ClinGen 1000Genomes
CA349690125 rs1313988751	501	Q>*		No	ClinGen TOPMed
CA349690119 rs1254782070	502	P>T		No	ClinGen gnomAD
rs1194138493 CA349690104	504	G>E		No	ClinGen gnomAD
CA61202954 rs372589188	505	S>C		No	ClinGen ESP TOPMed gnomAD
rs143157308 CA1975193	505	S>I		No	ClinGen ESP ExAC TOPMed gnomAD
CA349690099 rs143157308	505	S>N		No	ClinGen ESP ExAC TOPMed gnomAD
rs1033319539 CA61202953	506	S>R		No	ClinGen Ensembl
rs1194364252 CA349690093	506	S>S		No	ClinGen gnomAD

No associated diseases with P15336

3 regional properties for P15336

Type	Name	Position	InterPro Accession
domain	VHS domain	8 - 152	IPR002014
domain	GAT domain	219 - 307	IPR004152
domain	TOM1-like protein 2, VHS domain	12 - 148	IPR027429

Functions

		Description
EC Number
Subcellular Localization	Nucleus Cytoplasm Mitochondrion outer membrane	Shuttles between the cytoplasm and the nucleus and heterodimerization with JUN is essential for the nuclear localization Localization to the cytoplasm is observed under conditions of cellular stress and in disease states Localizes at the mitochondrial outer membrane in response to genotoxic stress Phosphorylation at Thr-52 is required for its nuclear localization and negatively regulates its mitochondrial localization Co-localizes with the MRN complex in the IR-induced foci (IRIF)
PANTHER Family	PTHR19304	CYCLIC-AMP RESPONSE ELEMENT BINDING PROTEIN
PANTHER Subfamily	PTHR19304:SF9	CYCLIC AMP-DEPENDENT TRANSCRIPTION FACTOR ATF-2
PANTHER Protein Class	DNA-binding transcription factor basic leucine zipper transcription factor
PANTHER Pathway Category	Ras Pathway ATF2 TGF-beta signaling pathway Co-activators corepressors Gonadotropin-releasing hormone receptor pathway ATF2 Apoptosis signaling pathway ATF Oxidative stress response ATF2 CCKR signaling map ATF2

9 GO annotations of cellular component

Name	Definition
CCAAT-binding factor complex	A heteromeric transcription factor complex that binds to the CCAAT-box upstream of promoters; functions as both an activator and a repressor, depending on its interacting cofactors. Typically trimeric consisting of NFYA, NFYB and NFYC subunits. In Saccharomyces, it activates the transcription of genes in response to growth in a nonfermentable carbon source and consists of four known subunits: HAP2, HAP3, HAP4 and HAP5.
chromatin	The ordered and organized complex of DNA, protein, and sometimes RNA, that forms the chromosome.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
H4 histone acetyltransferase complex	A protein complex which is capable of H4 histone acetyltransferase activity.
mitochondrial outer membrane	The outer, i.e. cytoplasm-facing, lipid bilayer of the mitochondrial envelope.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
RNA polymerase II transcription regulator complex	A transcription factor complex that acts at a regulatory region of a gene transcribed by RNA polymerase II.
site of double-strand break	A region of a chromosome at which a DNA double-strand break has occurred. DNA damage signaling and repair proteins accumulate at the lesion to respond to the damage and repair the DNA to form a continuous DNA helix.

21 GO annotations of molecular function

Name	Definition
cAMP response element binding	Binding to a cyclic AMP response element (CRE), a short palindrome-containing sequence found in the promoters of genes whose expression is regulated in response to cyclic AMP.
cAMP response element binding protein binding	Binding to a cAMP response element binding protein (a CREB protein).
cis-regulatory region sequence-specific DNA binding	Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by some RNA polymerase. The proximal promoter is in cis with and relatively close to the core promoter.
DNA-binding transcription activator activity, RNA polymerase II-specific	A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets transcribed by RNA polymerase II.
DNA-binding transcription factor activity	A transcription regulator activity that modulates transcription of gene sets via selective and non-covalent binding to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons.
DNA-binding transcription factor activity, RNA polymerase II-specific	A DNA-binding transcription factor activity that modulates the transcription of specific gene sets transcribed by RNA polymerase II.
H2B histone acetyltransferase activity	Catalysis of the reaction: acetyl-CoA + histone H2B L-lysine = CoA + histone H2B N6-acetyl-L-lysine.
H4 histone acetyltransferase activity	Catalysis of the reaction: acetyl-CoA + histone H4 = CoA + acetyl-histone H4.
histone acetyltransferase activity	Catalysis of the reaction: acetyl-CoA + histone = CoA + acetyl-histone.
identical protein binding	Binding to an identical protein or proteins.
leucine zipper domain binding	Binding to a leucine zipper domain, a protein secondary structure exhibiting a periodic repetition of leucine residues at every seventh position over a distance covering eight helical turns.
metal ion binding	Binding to a metal ion.
promoter-specific chromatin binding	Binding to a section of chromatin that is associated with gene promoter sequences of DNA.
protein heterodimerization activity	Binding to a nonidentical protein to form a heterodimer.
protein homodimerization activity	Binding to an identical protein to form a homodimer.
protein kinase binding	Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein-containing complex binding	Binding to a macromolecular complex.
RNA polymerase II cis-regulatory region sequence-specific DNA binding	Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by RNA polymerase II.
RNA polymerase II transcription regulatory region sequence-specific DNA binding	Binding to a specific sequence of DNA that is part of a regulatory region that controls the transcription of a gene or cistron by RNA polymerase II.
RNA polymerase II-specific DNA-binding transcription factor binding	Binding to a sequence-specific DNA binding RNA polymerase II transcription factor, any of the factors that interact selectively and non-covalently with a specific DNA sequence in order to modulate transcription.
sequence-specific double-stranded DNA binding	Binding to double-stranded DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA, e.g. promotor binding or rDNA binding.

53 GO annotations of biological process

Name	Definition
abducens nucleus development	The process whose specific outcome is the progression of the abducens nucleus over time, from its formation to the mature structure.
adipose tissue development	The process whose specific outcome is the progression of adipose tissue over time, from its formation to the mature structure. Adipose tissue is specialized tissue that is used to store fat.
amelogenesis	The process whose specific outcome is the formation of tooth enamel, occurring in two stages: secretory stage and maturation stage.
apoptotic process involved in development	Any apoptotic process that is involved in anatomical structure development.
BMP signaling pathway	The series of molecular signals initiated by the binding of a member of the BMP (bone morphogenetic protein) family to a receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
brainstem development	The progression of the brainstem from its formation to the mature structure. The brainstem is the part of the brain that connects the brain with the spinal cord.
cellular lipid metabolic process	The chemical reactions and pathways involving lipids, as carried out by individual cells.
cellular response to anisomycin	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an anisomycin stimulus.
cellular response to DNA damage stimulus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
cellular response to leucine starvation	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of deprivation of leucine.
cellular response to oxidative stress	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals.
cellular response to virus	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a virus.
detection of cell density	The series of events in which information about the density of cells in a population is received and converted into a molecular signal.
facial nucleus development	The process whose specific outcome is the progression of the facial nucleus over time, from its formation to the mature structure.
growth plate cartilage chondrocyte differentiation	The process in which a chondroblast acquires specialized structural and/or functional features of a chondrocyte that will contribute to the growth of a bone. A chondrocyte is a polymorphic cell that forms cartilage.
growth plate cartilage chondrocyte proliferation	The multiplication or reproduction of chondrocytes in a growing endochondral bone, resulting in the expansion of a cell population.
hematopoietic progenitor cell differentiation	The process in which precursor cell type acquires the specialized features of a hematopoietic progenitor cell, a class of cell types including myeloid progenitor cells and lymphoid progenitor cells.
hepatocyte apoptotic process	Any apoptotic process in a hepatocyte, the main structural component of the liver.
histone H2B acetylation	The modification of histone H2B by the addition of an acetyl group.
histone H4 acetylation	The modification of histone H4 by the addition of an acetyl group.
hypoglossal nucleus development	The process whose specific outcome is the progression of the hypoglossal nucleus over time, from its formation to the mature structure.
in utero embryonic development	The process whose specific outcome is the progression of the embryo in the uterus over time, from formation of the zygote in the oviduct, to birth. An example of this process is found in Mus musculus.
intrinsic apoptotic signaling pathway in response to hypoxia	The series of molecular signals in which an intracellular signal is conveyed to trigger the apoptotic death of a cell. The pathway is induced in response to hypoxia (lowered oxygen tension). Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level. The pathway ends when the execution phase of apoptosis is triggered.
JNK cascade	An intracellular protein kinase cascade containing at least a JNK (a MAPK), a JNKK (a MAPKK) and a JUN3K (a MAP3K). The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinases in the downstream tier to transmit a signal within a cell.
liver development	The process whose specific outcome is the progression of the liver over time, from its formation to the mature structure. The liver is an exocrine gland which secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes.
mitotic intra-S DNA damage checkpoint signaling	A mitotic cell cycle checkpoint that slows DNA synthesis in response to DNA damage by the prevention of new origin firing and the stabilization of slow replication fork progression.
motor neuron apoptotic process	Any apoptotic process in a motor neuron, an efferent neuron that passes from the central nervous system or a ganglion toward or to a muscle and conducts an impulse that causes movement.
mRNA transcription by RNA polymerase II	The cellular synthesis of messenger RNA (mRNA) from a DNA template by RNA polymerase II, originating at an RNA polymerase II promoter.
negative regulation of angiogenesis	Any process that stops, prevents, or reduces the frequency, rate or extent of angiogenesis.
negative regulation of epithelial cell proliferation	Any process that stops, prevents or reduces the rate or extent of epithelial cell proliferation.
negative regulation of transcription by RNA polymerase II	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II.
neurofilament cytoskeleton organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising neurofilaments and their associated proteins.
NK T cell differentiation	The process in which a precursor cell type acquires the specialized features of a NK T cell.
outflow tract morphogenesis	The process in which the anatomical structures of the outflow tract are generated and organized. The outflow tract is the portion of the heart through which blood flows into the arteries.
p38MAPK cascade	An intracellular protein kinase cascade containing at least a p38 MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinases in the downstream tier to transmit a signal within a cell.
peptidyl-threonine phosphorylation	The phosphorylation of peptidyl-threonine to form peptidyl-O-phospho-L-threonine.
positive regulation of cardiac muscle myoblast proliferation	Any process that activates or increases the frequency, rate or extent of cardiac muscle myoblast proliferation.
positive regulation of DNA-binding transcription factor activity	Any process that activates or increases the frequency, rate or extent of activity of a transcription factor, any factor involved in the initiation or regulation of transcription.
positive regulation of gene expression	Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
positive regulation of mitochondrial membrane permeability involved in apoptotic process	Any positive regulation of mitochondrial membrane permeability that is involved in apoptotic process.
positive regulation of neuron apoptotic process	Any process that activates or increases the frequency, rate or extent of cell death of neurons by apoptotic process.
positive regulation of protein phosphorylation	Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of transcription by RNA polymerase II	Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus	Any positive regulation of transcription from RNA polymerase II promoter that is involved in cellular response to chemical stimulus.
positive regulation of transforming growth factor beta2 production	Any process that activates or increases the frequency, rate, or extent of production of transforming growth factor-beta2.
protein import into nucleus	The directed movement of a protein from the cytoplasm to the nucleus.
regulation of transcription by RNA polymerase II	Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II.
regulation of transcription, DNA-templated	Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription.
response to organic cyclic compound	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an organic cyclic compound stimulus.
response to osmotic stress	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating an increase or decrease in the concentration of solutes outside the organism or cell.
response to water deprivation	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a water deprivation stimulus, prolonged deprivation of water.
vacuole organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a vacuole.
white fat cell differentiation	The process in which a relatively unspecialized cell acquires specialized features of a white adipocyte, an animal connective tissue cell involved in energy storage. White adipocytes have cytoplasmic lipids arranged in a unique vacuole.

8 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
O93602	ATF2	Cyclic AMP-dependent transcription factor ATF-2	Gallus gallus (Chicken)	SS
P15408	FOSL2	Fos-related antigen 2	Homo sapiens (Human)	PR
Q02930	CREB5	Cyclic AMP-responsive element-binding protein 5	Homo sapiens (Human)	SS
P17544	ATF7	Cyclic AMP-dependent transcription factor ATF-7	Homo sapiens (Human)	PR
P47930	Fosl2	Fos-related antigen 2	Mus musculus (Mouse)	PR
Q8R0S1	Atf7	Cyclic AMP-dependent transcription factor ATF-7	Mus musculus (Mouse)	PR
P16951	Atf2	Cyclic AMP-dependent transcription factor ATF-2	Mus musculus (Mouse)	SS
Q00969	Atf2	Cyclic AMP-dependent transcription factor ATF-2	Rattus norvegicus (Rat)	SS

10	20	30	40	50	60
MKFKLHVNSA	RQYKDLWNMS	DDKPFLCTAP	GCGQRFTNED	HLAVHKHKHE	MTLKFGPARN
70	80	90	100	110	120
DSVIVADQTP	TPTRFLKNCE	EVGLFNELAS	PFENEFKKAS	EDDIKKMPLD	LSPLATPIIR
130	140	150	160	170	180
SKIEEPSVVE	TTHQDSPLPH	PESTTSDEKE	VPLAQTAQPT	SAIVRPASLQ	VPNVLLTSSD
190	200	210	220	230	240
SSVIIQQAVP	SPTSSTVITQ	APSSNRPIVP	VPGPFPLLLH	LPNGQTMPVA	IPASITSSNV
250	260	270	280	290	300
HVPAAVPLVR	PVTMVPSVPG	IPGPSSPQPV	QSEAKMRLKA	ALTQQHPPVT	NGDTVKGHGS
310	320	330	340	350	360
GLVRTQSEES	RPQSLQQPAT	STTETPASPA	HTTPQTQSTS	GRRRRAANED	PDEKRRKFLE
370	380	390	400	410	420
RNRAAASRCR	QKRKVWVQSL	EKKAEDLSSL	NGQLQSEVTL	LRNEVAQLKQ	LLLAHKDCPV
430	440	450	460	470	480
TAMQKKSGYH	TADKDDSSED	ISVPSSPHTE	AIQHSSVSTS	NGVSSTSKAE	AVATSVLTQM
490	500
ADQSTEPALS	QIVMAPSSQS	QPSGS