Reviewed,
UniProtKB/Swiss-Prot Q02952 (AKA12_HUMAN)
Last modified
June 16, 2009.
Version 81.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
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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 |
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| 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 cortex Probable. Cytoplasm › cytoskeleton Probable. 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. Ref.9 Ref.10 Ref.11 |
| 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 targetingInferred from electronic annotation. Source: InterPro |
| Cellular component | cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell cytoskeletonInferred from electronic annotation. Source: UniProtKB-SubCell nucleusInferred from direct assay. Source: HPA plasma membraneInferred 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 Ref.9 | ||||||
| Modified residue | 253 | 1 | Phosphoserine Ref.10 | ||||||
| Modified residue | 283 | 1 | Phosphoserine Ref.10 | ||||||
| Modified residue | 286 | 1 | Phosphoserine Ref.10 | ||||||
| Modified residue | 312 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 374 | 1 | Phosphotyrosine By similarity | ||||||
| Modified residue | 388 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 483 | 1 | Phosphoserine By similarity | ||||||
| Modified residue | 505 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 565 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 566 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 568 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 569 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 598 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 612 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 627 | 1 | Phosphoserine Ref.10 | ||||||
| Modified residue | 629 | 1 | Phosphoserine Ref.10 | ||||||
| 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 Ref.11 | ||||||
| Modified residue | 887 | 1 | Phosphoserine Ref.11 | ||||||
| Modified residue | 1331 | 1 | Phosphoserine Ref.10 | ||||||
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. Ref.2 Ref.5 | VAR_035115 | |||||
| Natural variant | 216 | 1 | K → Q: dbSNP rs3734799. Ref.1 Ref.3 Ref.4 Ref.6 | VAR_035116 | |||||
| Natural variant | 240 | 1 | E → K in a colorectal cancer sample; somatic mutation. Ref.12 | VAR_035780 | |||||
| Natural variant | 920 | 1 | E → G: dbSNP rs13212161. Ref.3 | VAR_035117 | |||||
| Natural variant | 987 | 1 | A → S: dbSNP rs1042069. | VAR_056731 | |||||
| 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. Ref.3 | VAR_035120 | |||||
| Natural variant | 1600 | 1 | E → D: dbSNP rs3823310. Ref.4 | 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.3 | ||||||
| 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.4 | ||||||
| Sequence conflict | 1182 | 1 | A → T in CAH18338. Ref.4 | ||||||
| Sequence conflict | 1531 | 1 | E → EE in CAH18338. Ref.4 | ||||||
| Sequence conflict | 1531 | 1 | E → EE in BAE06085. Ref.3 | ||||||
| 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.4 | ||||||
| Sequence conflict | 1582 | 1 | V → M in AAA35931. Ref.7 | ||||||
| Sequence conflict | 1602 | 1 | Q → L in BAA19927. Ref.2 | ||||||
Sequences
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References
| « Hide '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), VARIANTS GLN-216 AND SER-987. 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] | "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. |
| [4] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANTS GLN-216; GLY-920 AND LYS-1355. Tissue: Testis. |
| [5] | "The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. Beck S.Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT LYS-117. |
| [6] | "Sequence of gravin cDNA isolated from a human umbilical vein endothelial cell library." Bowditch R.D., Ginsberg M.H. Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 43-1782, VARIANT GLN-216. Tissue: Umbilical vein endothelial cell. |
| [7] | "Molecular cloning and preliminary characterization of a novel cytoplasmic antigen recognized by myasthenia gravis sera." Gordon T., Grove B., Loftus J.C., O'Toole T., McMillan R., Lindstrom J., Ginsberg M.H. J. Clin. Invest. 90:992-999(1992) [PubMed: 1522245] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1478-1782. Tissue: Umbilical vein endothelial cell. |
| [8] | "Multiple promoters direct expression of three AKAP12 isoforms with distinct subcellular and tissue distribution profiles." Streb J.W., Kitchen C.M., Gelman I.H., Miano J.M. J. Biol. Chem. 279:56014-56023(2004) [PubMed: 15496411] [Abstract] Cited for: ALTERNATIVE SPLICING. |
| [9] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219; SER-312; SER-565; SER-566; SER-568; SER-569; SER-598 AND SER-612, MASS SPECTROMETRY. Tissue: Epithelium. |
| [10] | "Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-253; SER-283; SER-286; SER-627; SER-629 AND SER-1331, MASS SPECTROMETRY. |
| [11] | "ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-388; SER-505; SER-732 AND SER-887, MASS SPECTROMETRY. |
| [12] | "The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LYS-240. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| U81607 mRNA. Translation: AAC51366.1. AB003476 mRNA. Translation: BAA19927.1. AB210003 mRNA. Translation: BAE06085.1. Different initiation. CR749527 mRNA. Translation: CAH18338.1. AL590413, AL033392, AL356535 Genomic DNA. Translation: CAI13590.1. AL356535, AL033392, AL590413 Genomic DNA. Translation: CAI16151.1. AL033392, AL356535, AL590413 Genomic DNA. Translation: CAI20467.1. AL590413, AL033392 Genomic DNA. Translation: CAI13591.1. AL033392, AL590413 Genomic DNA. Translation: CAI20468.1. AF001504 mRNA. Translation: AAB58938.1. M96322 mRNA. Translation: AAA35931.1. | |
| IPI | IPI00217683. IPI00237884. IPI00867627. |
| PIR | A43922. JW0057. |
| RefSeq | NP_653080.1. |
| UniGene | Hs.371240 |
3D structure databases | |
| ModBase | Search... |
PTM databases | |
| PhosphoSite | Q02952. |
Proteomic databases | |
| PRIDE | Q02952. |
Genome annotation databases | |
| Ensembl | ENSG00000131016. Homo sapiens. [Contig view] |
| GeneID | 9590. |
Organism-specific databases | |
| GeneCards | GC06P151653. |
| H-InvDB | HIX0025002. |
| HGNC | HGNC:370. AKAP12. |
| HPA | HPA006344. |
| MIM | 604698. gene. |
| PharmGKB | PA24664. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOVERGEN | Q02952. |
Gene expression databases | |
| ArrayExpress | Q02952. |
| Bgee | Q02952. |
| CleanEx | HS_AKAP12. |
| GermOnline | ENSG00000131016. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR001573. Pkinase-A_anch_WSK-motif. IPR018459. RII_binding_1. [Graphical view] |
| Pfam | PF10522. RII_binding_1. 1 hit. PF03832. WSK. 3 hits. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 35991. |
| SOURCE | Search... |
Entry information
| Entry name | AKA12_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q02952 Secondary accession number(s): O00310 Q99970 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 6 Human chromosome 6: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


