Reviewed, UniProtKB/Swiss-Prot Q02952 (AKA12_HUMAN)

Names and origin

Protein names

Recommended name:
    A-kinase anchor protein 12
Alternative name(s):
    A-kinase anchor protein 250 kDa
      Short name=AKAP 250
    Gravin
    Myasthenia gravis autoantigen

Gene names

Name:	AKAP12
Synonyms:	AKAP250

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1782 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) and protein kinase C (PKC).
Subunit structure	Binds to dimeric RII-alpha regulatory subunit of PKC.
Subcellular location	Cytoplasm › cell cortexProbable. Cytoplasm › cytoskeletonProbable. Note= May be part of the cortical cytoskeleton.
Tissue specificity	Expressed in endothelial cells, cultured fibroblasts and osteosarcoma, but not in platelets, leukocytes, monocytic cell lines or peripherical blood cells.
Induction	Activated by lysophosphatidylcholine (lysoPC).
Domain	Polybasic regions located between residues 266 and 557 are involved in binding PKC.
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR.
Involvement in disease	Antibodies to the C-terminal of gravin can be produced by patients with myasthenia gravis (MG).
Sequence similarities	Contains 3 AKAP domains.

Ontologies

Keywords
Cellular component	Cytoplasm Cytoskeleton
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Traceable author statement. Source: ProtInc protein targeting Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Traceable author statement. Source: ProtInc cytoskeleton Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular function	protein kinase A binding Traceable author statement. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q02952-1)

Also known as: Alpha;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q02952-2)

Also known as: Beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: Missing.
     99-106: EEEVIVTE → MLGTITIT

Isoform 3 (identifier: Q02952-3)

Also known as: Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: Missing.
     106-106: E → M

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1782	1782	A-kinase anchor protein 12		PRO_0000064519
Regions
	Domain	604 – 634	31	AKAP 1
	Domain	753 – 783	31	AKAP 2
	Domain	798 – 828	31	AKAP 3
	Region	266 – 557	292	Involved in PKC-binding Probable
	Region	1541 – 1554	14	RII-binding Probable
	Compositional bias	98 – 101	4	Poly-Glu
Amino acid modifications
	Modified residue	19	1	Phosphoserine By similarity
	Modified residue	219	1	Phosphoserine
	Modified residue	253	1	Phosphoserine
	Modified residue	283	1	Phosphoserine
	Modified residue	286	1	Phosphoserine
	Modified residue	312	1	Phosphoserine
	Modified residue	388	1	Phosphoserine
	Modified residue	483	1	Phosphoserine By similarity
	Modified residue	505	1	Phosphoserine
	Modified residue	565	1	Phosphoserine
	Modified residue	566	1	Phosphoserine
	Modified residue	568	1	Phosphoserine
	Modified residue	569	1	Phosphoserine
	Modified residue	598	1	Phosphoserine
	Modified residue	612	1	Phosphoserine
	Modified residue	627	1	Phosphoserine
	Modified residue	629	1	Phosphoserine
	Modified residue	645	1	Phosphoserine By similarity
	Modified residue	646	1	Phosphothreonine By similarity
	Modified residue	648	1	Phosphoserine By similarity
	Modified residue	696	1	Phosphoserine By similarity
	Modified residue	697	1	Phosphoserine By similarity
	Modified residue	698	1	Phosphoserine By similarity
	Modified residue	732	1	Phosphoserine
	Modified residue	887	1	Phosphoserine
	Modified residue	1331	1	Phosphoserine
Natural variations
	Alternative sequence	1 – 105	105	Missing in isoform 3.		VSP_028133
	Alternative sequence	1 – 98	98	Missing in isoform 2.		VSP_004110
	Alternative sequence	99 – 106	8	EEEVIVTE → MLGTITIT in isoform 2.		VSP_004111
	Alternative sequence	106	1	E → M in isoform 3.		VSP_028134
	Natural variant	117	1	E → K: dbSNP rs10872670.		VAR_035115
	Natural variant	216	1	K → Q: dbSNP rs3734799.		VAR_035116
	Natural variant	240	1	E → K in a colorectal cancer sample; somatic mutation.		VAR_035780
	Natural variant	920	1	E → G: dbSNP rs13212161.		VAR_035117
	Natural variant	1096	1	V → I: dbSNP rs3734797.		VAR_035118
	Natural variant	1296	1	R → L: dbSNP rs9478198.		VAR_035119
	Natural variant	1355	1	E → K: dbSNP rs12201388.		VAR_035120
	Natural variant	1600	1	E → D: dbSNP rs3823310.		VAR_035121
	Natural variant	1689	1	E → D: dbSNP rs3734795.		VAR_035122
Experimental info
	Sequence conflict	142 – 145	4	TPEI → NRN in AAC51366. Ref.1
	Sequence conflict	423	1	T → I in BAE06085. Ref.4
	Sequence conflict	449	1	E → G in AAC51366. Ref.1
	Sequence conflict	695	1	G → R in AAC51366. Ref.1
	Sequence conflict	868	1	S → G in AAC51366. Ref.1
	Sequence conflict	946	1	E → G in CAH18338. Ref.3
	Sequence conflict	987	1	A → S in AAC51366. Ref.1
	Sequence conflict	1182	1	A → T in CAH18338. Ref.3
	Sequence conflict	1531	1	E → EE in CAH18338. Ref.3
	Sequence conflict	1531	1	E → EE in BAE06085. Ref.4
	Sequence conflict	1531	1	E → EE in AAB58938. Ref.6
	Sequence conflict	1531	1	E → EE in AAA35931. Ref.7
	Sequence conflict	1582	1	V → M in CAH18338. Ref.3
	Sequence conflict	1582	1	V → M in AAA35931. Ref.7
	Sequence conflict	1602	1	Q → L in BAA19927. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Alpha) [UniParc]. Last modified October 2, 2007. Version 3. Checksum: B68AA70EF351FE5D	FASTA	1,782	191,483
	10 20 30 40 50 60 MGAGSSTEQR SPEQPPEGSS TPAEPEPSGG GPSAEAAPDT TADPAIAASD PATKLLQKNG 70 80 90 100 110 120 QLSTINGVAE QDELSLQEGD LNGQKGALNG QGALNSQEEE EVIVTEVGQR DSEDVSERDS 130 140 150 160 170 180 DKEMATKSAV VHDITDDGQE ETPEIIEQIP SSESNLEELT QPTESQANDI GFKKVFKFVG 190 200 210 220 230 240 FKFTVKKDKT EKPDTVQLLT VKKDEGEGAA GAGDHKDPSL GAGEAASKES EPKQSTEKPE 250 260 270 280 290 300 ETLKREQSHA EISPPAESGQ AVEECKEEGE EKQEKEPSKS AESPTSPVTS ETGSTFKKFF 310 320 330 340 350 360 TQGWAGWRKK TSFRKPKEDE VEASEKKKEQ EPEKVDTEED GKAEVASEKL TASEQAHPQE 370 380 390 400 410 420 PAESAHEPRL SAEYEKVELP SEEQVSGSQG PSEEKPAPLA TEVFDEKIEV HQEEVVAEVH 430 440 450 460 470 480 VSTVEERTEE QKTEVEETAG SVPAEELVEM DAEPQEAEPA KELVKLKETC VSGEDPTQGA 490 500 510 520 530 540 DLSPDEKVLS KPPEGVVSEV EMLSSQERMK VQGSPLKKLF TSTGLKKLSG KKQKGKRGGG 550 560 570 580 590 600 DEESGEHTQV PADSPDSQEE QKGESSASSP EEPEEITCLE KGLAEVQQDG EAEEGATSDG 610 620 630 640 650 660 EKKREGVTPW ASFKKMVTPK KRVRRPSESD KEDELDKVKS ATLSSTESTA SEMQEEMKGS 670 680 690 700 710 720 VEEPKPEEPK RKVDTSVSWE ALICVGSSKK RARRGSSSDE EGGPKAMGGD HQKADEAGKD 730 740 750 760 770 780 KETGTDGILA GSQEHDPGQG SSSPEQAGSP TEGEGVSTWE SFKRLVTPRK KSKSKLEEKS 790 800 810 820 830 840 EDSIAGSGVE HSTPDTEPGK EESWVSIKKF IPGRRKKRPD GKQEQAPVED AGPTGANEDD 850 860 870 880 890 900 SDVPAVVPLS EYDAVEREKM EAQQAQKSAE QPEQKAATEV SKELSESQVH MMAAAVADGT 910 920 930 940 950 960 RAATIIEERS PSWISASVTE PLEQVEAEAA LLTEEVLERE VIAEEEPPTV TEPLPENREA 970 980 990 1000 1010 1020 RGDTVVSEAE LTPEAVTAAE TAGPLGAEEG TEASAAEETT EMVSAVSQLT DSPDTTEEAT 1030 1040 1050 1060 1070 1080 PVQEVEGGVP DIEEQERRTQ EVLQAVAEKV KEESQLPGTG GPEDVLQPVQ RAEAERPEEQ 1090 1100 1110 1120 1130 1140 AEASGLKKET DVVLKVDAQE AKTEPFTQGK VVGQTTPESF EKAPQVTESI ESSELVTTCQ 1150 1160 1170 1180 1190 1200 AETLAGVKSQ EMVMEQAIPP DSVETPTDSE TDGSTPVADF DAPGTTQKDE IVEIHEENEV 1210 1220 1230 1240 1250 1260 ASGTQSGGTE AEAVPAQKER PPAPSSFVFQ EETKEQSKME DTLEHTDKEV SVETVSILSK 1270 1280 1290 1300 1310 1320 TEGTQEADQY ADEKTKDVPF FEGLEGSIDT GITVSREKVT EVALKGEGTE EAECKKDDAL 1330 1340 1350 1360 1370 1380 ELQSHAKSPP SPVEREMVVQ VEREKTEAEP THVNEEKLEH ETAVTVSEEV SKQLLQTVNV 1390 1400 1410 1420 1430 1440 PIIDGAKEVS SLEGSPPPCL GQEEAVCTKI QVQSSEASFT LTAAAEEEKV LGETANILET 1450 1460 1470 1480 1490 1500 GETLEPAGAH LVLEEKSSEK NEDFAAHPGE DAVPTGPDCQ AKSTPVIVSA TTKKGLSSDL 1510 1520 1530 1540 1550 1560 EGEKTTSLKW KSDEVDEQVA CQEVKVSVAI EDLEPENGIL ELETKSSKLV QNIIQTAVDQ 1570 1580 1590 1600 1610 1620 FVRTEETATE MLTSELQTQA HVIKADSQDA GQETEKEGEE PQASAQDETP ITSAKEESES 1630 1640 1650 1660 1670 1680 TAVGQAHSDI SKDMSEASEK TMTVEVEGST VNDQQLEEVV LPSEEEGGGA GTKSVPEDDG 1690 1700 1710 1720 1730 1740 HALLAERIEK SLVEPKEDEK GDDVDDPENQ NSALADTDAS GGLTKESPDT NGPKQKEKED 1750 1760 1770 1780 AQEVELQEGK VHSESDKAIT PQAQEELQKQ ERESAKSELT ES
	Isoform 2 (Beta) [UniParc]. Checksum: 555DF0E8D87F1E1B		1,684	181,690
	10 20 30 40 50 60 MLGTITITVG QRDSEDVSER DSDKEMATKS AVVHDITDDG QEETPEIIEQ IPSSESNLEE 70 80 90 100 110 120 LTQPTESQAN DIGFKKVFKF VGFKFTVKKD KTEKPDTVQL LTVKKDEGEG AAGAGDHKDP 130 140 150 160 170 180 SLGAGEAASK ESEPKQSTEK PEETLKREQS HAEISPPAES GQAVEECKEE GEEKQEKEPS 190 200 210 220 230 240 KSAESPTSPV TSETGSTFKK FFTQGWAGWR KKTSFRKPKE DEVEASEKKK EQEPEKVDTE 250 260 270 280 290 300 EDGKAEVASE KLTASEQAHP QEPAESAHEP RLSAEYEKVE LPSEEQVSGS QGPSEEKPAP 310 320 330 340 350 360 LATEVFDEKI EVHQEEVVAE VHVSTVEERT EEQKTEVEET AGSVPAEELV EMDAEPQEAE 370 380 390 400 410 420 PAKELVKLKE TCVSGEDPTQ GADLSPDEKV LSKPPEGVVS EVEMLSSQER MKVQGSPLKK 430 440 450 460 470 480 LFTSTGLKKL SGKKQKGKRG GGDEESGEHT QVPADSPDSQ EEQKGESSAS SPEEPEEITC 490 500 510 520 530 540 LEKGLAEVQQ DGEAEEGATS DGEKKREGVT PWASFKKMVT PKKRVRRPSE SDKEDELDKV 550 560 570 580 590 600 KSATLSSTES TASEMQEEMK GSVEEPKPEE PKRKVDTSVS WEALICVGSS KKRARRGSSS 610 620 630 640 650 660 DEEGGPKAMG GDHQKADEAG KDKETGTDGI LAGSQEHDPG QGSSSPEQAG SPTEGEGVST 670 680 690 700 710 720 WESFKRLVTP RKKSKSKLEE KSEDSIAGSG VEHSTPDTEP GKEESWVSIK KFIPGRRKKR 730 740 750 760 770 780 PDGKQEQAPV EDAGPTGANE DDSDVPAVVP LSEYDAVERE KMEAQQAQKS AEQPEQKAAT 790 800 810 820 830 840 EVSKELSESQ VHMMAAAVAD GTRAATIIEE RSPSWISASV TEPLEQVEAE AALLTEEVLE 850 860 870 880 890 900 REVIAEEEPP TVTEPLPENR EARGDTVVSE AELTPEAVTA AETAGPLGAE EGTEASAAEE 910 920 930 940 950 960 TTEMVSAVSQ LTDSPDTTEE ATPVQEVEGG VPDIEEQERR TQEVLQAVAE KVKEESQLPG 970 980 990 1000 1010 1020 TGGPEDVLQP VQRAEAERPE EQAEASGLKK ETDVVLKVDA QEAKTEPFTQ GKVVGQTTPE 1030 1040 1050 1060 1070 1080 SFEKAPQVTE SIESSELVTT CQAETLAGVK SQEMVMEQAI PPDSVETPTD SETDGSTPVA 1090 1100 1110 1120 1130 1140 DFDAPGTTQK DEIVEIHEEN EVASGTQSGG TEAEAVPAQK ERPPAPSSFV FQEETKEQSK 1150 1160 1170 1180 1190 1200 MEDTLEHTDK EVSVETVSIL SKTEGTQEAD QYADEKTKDV PFFEGLEGSI DTGITVSREK 1210 1220 1230 1240 1250 1260 VTEVALKGEG TEEAECKKDD ALELQSHAKS PPSPVEREMV VQVEREKTEA EPTHVNEEKL 1270 1280 1290 1300 1310 1320 EHETAVTVSE EVSKQLLQTV NVPIIDGAKE VSSLEGSPPP CLGQEEAVCT KIQVQSSEAS 1330 1340 1350 1360 1370 1380 FTLTAAAEEE KVLGETANIL ETGETLEPAG AHLVLEEKSS EKNEDFAAHP GEDAVPTGPD 1390 1400 1410 1420 1430 1440 CQAKSTPVIV SATTKKGLSS DLEGEKTTSL KWKSDEVDEQ VACQEVKVSV AIEDLEPENG 1450 1460 1470 1480 1490 1500 ILELETKSSK LVQNIIQTAV DQFVRTEETA TEMLTSELQT QAHVIKADSQ DAGQETEKEG 1510 1520 1530 1540 1550 1560 EEPQASAQDE TPITSAKEES ESTAVGQAHS DISKDMSEAS EKTMTVEVEG STVNDQQLEE 1570 1580 1590 1600 1610 1620 VVLPSEEEGG GAGTKSVPED DGHALLAERI EKSLVEPKED EKGDDVDDPE NQNSALADTD 1630 1640 1650 1660 1670 1680 ASGGLTKESP DTNGPKQKEK EDAQEVELQE GKVHSESDKA ITPQAQEELQ KQERESAKSE LTES
	Isoform 3 (Gamma) [UniParc]. Checksum: E8247A662D5F825E		1,677	180,991
	10 20 30 40 50 60 MVGQRDSEDV SERDSDKEMA TKSAVVHDIT DDGQEETPEI IEQIPSSESN LEELTQPTES 70 80 90 100 110 120 QANDIGFKKV FKFVGFKFTV KKDKTEKPDT VQLLTVKKDE GEGAAGAGDH KDPSLGAGEA 130 140 150 160 170 180 ASKESEPKQS TEKPEETLKR EQSHAEISPP AESGQAVEEC KEEGEEKQEK EPSKSAESPT 190 200 210 220 230 240 SPVTSETGST FKKFFTQGWA GWRKKTSFRK PKEDEVEASE KKKEQEPEKV DTEEDGKAEV 250 260 270 280 290 300 ASEKLTASEQ AHPQEPAESA HEPRLSAEYE KVELPSEEQV SGSQGPSEEK PAPLATEVFD 310 320 330 340 350 360 EKIEVHQEEV VAEVHVSTVE ERTEEQKTEV EETAGSVPAE ELVEMDAEPQ EAEPAKELVK 370 380 390 400 410 420 LKETCVSGED PTQGADLSPD EKVLSKPPEG VVSEVEMLSS QERMKVQGSP LKKLFTSTGL 430 440 450 460 470 480 KKLSGKKQKG KRGGGDEESG EHTQVPADSP DSQEEQKGES SASSPEEPEE ITCLEKGLAE 490 500 510 520 530 540 VQQDGEAEEG ATSDGEKKRE GVTPWASFKK MVTPKKRVRR PSESDKEDEL DKVKSATLSS 550 560 570 580 590 600 TESTASEMQE EMKGSVEEPK PEEPKRKVDT SVSWEALICV GSSKKRARRG SSSDEEGGPK 610 620 630 640 650 660 AMGGDHQKAD EAGKDKETGT DGILAGSQEH DPGQGSSSPE QAGSPTEGEG VSTWESFKRL 670 680 690 700 710 720 VTPRKKSKSK LEEKSEDSIA GSGVEHSTPD TEPGKEESWV SIKKFIPGRR KKRPDGKQEQ 730 740 750 760 770 780 APVEDAGPTG ANEDDSDVPA VVPLSEYDAV EREKMEAQQA QKSAEQPEQK AATEVSKELS 790 800 810 820 830 840 ESQVHMMAAA VADGTRAATI IEERSPSWIS ASVTEPLEQV EAEAALLTEE VLEREVIAEE 850 860 870 880 890 900 EPPTVTEPLP ENREARGDTV VSEAELTPEA VTAAETAGPL GAEEGTEASA AEETTEMVSA 910 920 930 940 950 960 VSQLTDSPDT TEEATPVQEV EGGVPDIEEQ ERRTQEVLQA VAEKVKEESQ LPGTGGPEDV 970 980 990 1000 1010 1020 LQPVQRAEAE RPEEQAEASG LKKETDVVLK VDAQEAKTEP FTQGKVVGQT TPESFEKAPQ 1030 1040 1050 1060 1070 1080 VTESIESSEL VTTCQAETLA GVKSQEMVME QAIPPDSVET PTDSETDGST PVADFDAPGT 1090 1100 1110 1120 1130 1140 TQKDEIVEIH EENEVASGTQ SGGTEAEAVP AQKERPPAPS SFVFQEETKE QSKMEDTLEH 1150 1160 1170 1180 1190 1200 TDKEVSVETV SILSKTEGTQ EADQYADEKT KDVPFFEGLE GSIDTGITVS REKVTEVALK 1210 1220 1230 1240 1250 1260 GEGTEEAECK KDDALELQSH AKSPPSPVER EMVVQVEREK TEAEPTHVNE EKLEHETAVT 1270 1280 1290 1300 1310 1320 VSEEVSKQLL QTVNVPIIDG AKEVSSLEGS PPPCLGQEEA VCTKIQVQSS EASFTLTAAA 1330 1340 1350 1360 1370 1380 EEEKVLGETA NILETGETLE PAGAHLVLEE KSSEKNEDFA AHPGEDAVPT GPDCQAKSTP 1390 1400 1410 1420 1430 1440 VIVSATTKKG LSSDLEGEKT TSLKWKSDEV DEQVACQEVK VSVAIEDLEP ENGILELETK 1450 1460 1470 1480 1490 1500 SSKLVQNIIQ TAVDQFVRTE ETATEMLTSE LQTQAHVIKA DSQDAGQETE KEGEEPQASA 1510 1520 1530 1540 1550 1560 QDETPITSAK EESESTAVGQ AHSDISKDMS EASEKTMTVE VEGSTVNDQQ LEEVVLPSEE 1570 1580 1590 1600 1610 1620 EGGGAGTKSV PEDDGHALLA ERIEKSLVEP KEDEKGDDVD DPENQNSALA DTDASGGLTK 1630 1640 1650 1660 1670 ESPDTNGPKQ KEKEDAQEVE LQEGKVHSES DKAITPQAQE ELQKQERESA KSELTES

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Gravin, an autoantigen recognized by serum from myasthenia gravis patients, is a kinase scaffold protein." Nauert J.B., Klauck T.M., Langeberg L.K., Scott J.D. Curr. Biol. 7:52-62(1997) [PubMed: 9000000] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLN-216. Tissue: Heart.
[2]	"Changes of gene expression by lysophosphatidylcholine in vascular endothelial cells: 12 up-regulated distinct genes including 5 cell growth-related, 3 thrombosis-related, and 4 others." Sato N., Kokame K., Shimokado K., Kato H., Miyata T. J. Biochem. 123:1119-1126(1998) [PubMed: 9604001] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LYS-117. Tissue: Umbilical vein endothelial cell.
[3]	The German cDNA consortium Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANTS GLN-216; GLY-920 AND LYS-1355. Tissue: Testis.
[4]	"Preparation of a set of expression-ready clones of mammalian long cDNAs encoding large proteins by the ORF trap cloning method." Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., Okazaki N., Koga H., Nagase T., Ohara O. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANTS GLN-216 AND ASP-1600. Tissue: Brain.
[5]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J.,