Q6P1N0 (C2D1A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Coiled-coil and C2 domain-containing protein 1A

Alternative name(s):
Akt kinase-interacting protein 1
Five prime repressor element under dual repression-binding protein 1
Short name=FRE under dual repression-binding protein 1
Short name=Freud-1
Putative NF-kappa-B-activating protein 023N

Gene names

Name:	CC2D1A
Synonyms:	AKI1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	951 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Transcription factor that binds specifically to the DRE (dual repressor element) and represses HTR1A gene transcription in neuronal cells. The combination of calcium and ATP specifically inactivates the binding with FRE. May play a role in the altered regulation of HTR1A associated with anxiety and major depression. Mediates HDAC-independent repression of HTR1A promoter in neuronal cell. Performs essential function in controlling functional maturation of synapses By similarity. Plays distinct roles depending on its localization. When cytoplasmic, acts as a scaffold protein in the PI3K/PDK1/AKT pathway. Repressor of HTR1A when nuclear. In the centrosome, regulates spindle pole localization of the cohesin subunit SCC1/RAD21, thereby mediating centriole cohesion during mitosis. Ref.10
Subcellular location	Cytoplasm. Nucleus. Cytoplasm › cytoskeleton › centrosome Ref.6 Ref.10.
Domain	The C2 domain is required for the repression By similarity.
Post-translational modification	Phosphorylation on Ser-208 by CDK1 promotes spindle pole localization and association with SCC1/RAD21.
Involvement in disease	Mental retardation, autosomal recessive 3 (MRT3) [MIM:608443]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period. Non-syndromic mental retardation patients do not manifest other clinical signs. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.6
Sequence similarities	Belongs to the CC2D1 family. Contains 1 C2 domain.
Sequence caution	The sequence BAA91029.1 differs from that shown. Reason: Aberrant splicing. The sequence BAB15464.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Cytoskeleton Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Mental retardation
Domain	Coiled coil
Ligand	DNA-binding
Molecular function	Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype Ref.2. Source: UniProtKB
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell microtubule organizing center Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	RNA polymerase II core promoter proximal region sequence-specific DNA binding Inferred from electronic annotation. Source: Compara RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Inferred from electronic annotation. Source: Compara signal transducer activity Inferred from mutant phenotype Ref.2. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q6P1N0-1)

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: Q6P1N0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     819-819: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 951	951	Coiled-coil and C2 domain-containing protein 1A		PRO_0000239609
Regions
	Domain	642 – 755	114	C2
	Coiled coil	346 – 392	47	Potential
	Coiled coil	484 – 517	34	Potential
	Compositional bias	192 – 345	154	Pro-rich
Amino acid modifications
	Modified residue	204	1	Phosphothreonine Ref.9
	Modified residue	208	1	Phosphoserine; by CDK1 Ref.7 Ref.9 Ref.10 Ref.11
	Modified residue	253	1	Phosphoserine Ref.9
	Modified residue	455	1	Phosphoserine Ref.9 Ref.11 Ref.13
Natural variations
	Alternative sequence	819	1	Missing in isoform 2.		VSP_019242
	Natural variant	339	1	T → P. Corresponds to variant rs11883041 [ dbSNP | Ensembl ].		VAR_026670
	Natural variant	635	1	T → S. Corresponds to variant rs2290663 [ dbSNP | Ensembl ].		VAR_026671
	Natural variant	801	1	T → M. Corresponds to variant rs2305777 [ dbSNP | Ensembl ].		VAR_026672
Experimental info
	Sequence conflict	646	1	I → V in AAN04488. Ref.1
	Sequence conflict	824	1	K → E in BAC77355. Ref.2
	Sequence conflict	837	1	S → P in BAC77355. Ref.2
	Sequence conflict	906	1	A → T in BAC77355. Ref.2
	Sequence conflict	943	1	E → G in BAC77355. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: 04D80124FC47729A	FASTA	951	104,062
	10 20 30 40 50 60 MHKRKGPPGP PGRGAAAARQ LGLLVDLSPD GLMIPEDGAN DEELEAEFLA LVGGQPPALE 70 80 90 100 110 120 KLKGKGPLPM EAIEKMASLC MRDPDEDEEE GTDEDDLEAD DDLLAELNEV LGEEQKASET 130 140 150 160 170 180 PPPVAQPKPE APHPGLETTL QERLALYQTA IESARQAGDS AKMRRYDRGL KTLENLLASI 190 200 210 220 230 240 RKGNAIDEAD IPPPVAIGKG PASTPTYSPA PTQPAPRIAS APEPRVTLEG PSATAPASSP 250 260 270 280 290 300 GLAKPQMPPG PCSPGPLAQL QSRQRDYKLA ALHAKQQGDT TAAARHFRVA KSFDAVLEAL 310 320 330 340 350 360 SRGEPVDLSC LPPPPDQLPP DPPSPPSQPP TPATAPSTTE VPPPPRTLLE ALEQRMERYQ 370 380 390 400 410 420 VAAAQAKSKG DQRKARMHER IVKQYQDAIR AHKAGRAVDV AELPVPPGFP PIQGLEATKP 430 440 450 460 470 480 TQQSLVGVLE TAMKLANQDE GPEDEEDEVP KKQNSPVAPT AQPKAPPSRT PQSGSAPTAK 490 500 510 520 530 540 APPKATSTRA QQQLAFLEGR KKQLLQAALR AKQKNDVEGA KMHLRQAKGL EPMLEASRNG 550 560 570 580 590 600 LPVDITKVPP APVNKDDFAL VQRPGPGLSQ EAARRYGELT KLIRQQHEMC LNHSNQFTQL 610 620 630 640 650 660 GNITETTKFE KLAEDCKRSM DILKQAFVRG LPTPTARFEQ RTFSVIKIFP DLSSNDMLLF 670 680 690 700 710 720 IVKGINLPTP PGLSPGDLDV FVRFDFPYPN VEEAQKDKTS VIKNTDSPEF KEQFKLCINR 730 740 750 760 770 780 SHRGFRRAIQ TKGIKFEVVH KGGLFKTDRV LGTAQLKLDA LEIACEVREI LEVLDGRRPT 790 800 810 820 830 840 GGRLEVMVRI REPLTAQQLE TTTERWLVID PVPAAVPTQV AGPKGKAPPV PAPARESGNR 850 860 870 880 890 900 SARPLHSLSV LAFDQERLER KILALRQARR PVPPEVAQQY QDIMQRSQWQ RAQLEQGGVG 910 920 930 940 950 IRREYAAQLE RQLQFYTEAA RRLGNDGSRD AAKEALYRRN LVESELQRLR R
	Isoform 2 [UniParc]. Checksum: 4A6B9FF39DECF316	FASTA	950	103,934
	10 20 30 40 50 60 MHKRKGPPGP PGRGAAAARQ LGLLVDLSPD GLMIPEDGAN DEELEAEFLA LVGGQPPALE 70 80 90 100 110 120 KLKGKGPLPM EAIEKMASLC MRDPDEDEEE GTDEDDLEAD DDLLAELNEV LGEEQKASET 130 140 150 160 170 180 PPPVAQPKPE APHPGLETTL QERLALYQTA IESARQAGDS AKMRRYDRGL KTLENLLASI 190 200 210 220 230 240 RKGNAIDEAD IPPPVAIGKG PASTPTYSPA PTQPAPRIAS APEPRVTLEG PSATAPASSP 250 260 270 280 290 300 GLAKPQMPPG PCSPGPLAQL QSRQRDYKLA ALHAKQQGDT TAAARHFRVA KSFDAVLEAL 310 320 330 340 350 360 SRGEPVDLSC LPPPPDQLPP DPPSPPSQPP TPATAPSTTE VPPPPRTLLE ALEQRMERYQ 370 380 390 400 410 420 VAAAQAKSKG DQRKARMHER IVKQYQDAIR AHKAGRAVDV AELPVPPGFP PIQGLEATKP 430 440 450 460 470 480 TQQSLVGVLE TAMKLANQDE GPEDEEDEVP KKQNSPVAPT AQPKAPPSRT PQSGSAPTAK 490 500 510 520 530 540 APPKATSTRA QQQLAFLEGR KKQLLQAALR AKQKNDVEGA KMHLRQAKGL EPMLEASRNG 550 560 570 580 590 600 LPVDITKVPP APVNKDDFAL VQRPGPGLSQ EAARRYGELT KLIRQQHEMC LNHSNQFTQL 610 620 630 640 650 660 GNITETTKFE KLAEDCKRSM DILKQAFVRG LPTPTARFEQ RTFSVIKIFP DLSSNDMLLF 670 680 690 700 710 720 IVKGINLPTP PGLSPGDLDV FVRFDFPYPN VEEAQKDKTS VIKNTDSPEF KEQFKLCINR 730 740 750 760 770 780 SHRGFRRAIQ TKGIKFEVVH KGGLFKTDRV LGTAQLKLDA LEIACEVREI LEVLDGRRPT 790 800 810 820 830 840 GGRLEVMVRI REPLTAQQLE TTTERWLVID PVPAAVPTVA GPKGKAPPVP APARESGNRS 850 860 870 880 890 900 ARPLHSLSVL AFDQERLERK ILALRQARRP VPPEVAQQYQ DIMQRSQWQR AQLEQGGVGI 910 920 930 940 950 RREYAAQLER QLQFYTEAAR RLGNDGSRDA AKEALYRRNL VESELQRLRR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Guo J.H., Chen L., Yu L. Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Kidney.
[2]	"Large-scale identification and characterization of human genes that activate NF-kappaB and MAPK signaling pathways." Matsuda A., Suzuki Y., Honda G., Muramatsu S., Matsuzaki O., Nagano Y., Doi T., Shimotohno K., Harada T., Nishida E., Hayashi H., Sugano S. Oncogene 22:3307-3318(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung fibroblast.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 254-606 AND 622-951 (ISOFORM 1). Tissue: Ovary.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Ovary.
[5]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]	"The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non-syndromic mental retardation." Basel-Vanagaite L., Attia R., Yahav M., Ferland R.J., Anteki L., Walsh C.A., Olender T., Straussberg R., Magal N., Taub E., Drasinover V., Alkelai A., Bercovich D., Rechavi G., Simon A.J., Shohat M. J. Med. Genet. 43:203-210(2006) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INVOLVEMENT IN MRT3.
[7]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-208, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-204; SER-208; SER-253 AND SER-455, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"Mitotic phosphorylation of Aki1 at Ser208 by cyclin B1-Cdk1 complex." Nakamura A., Naito M., Arai H., Fujita N. Biochem. Biophys. Res. Commun. 393:872-876(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-208 BY CDK1, SUBCELLULAR LOCATION.
[11]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-208 AND SER-455, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-455, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF536205 mRNA. Translation: AAN04488.1. AB097002 mRNA. Translation: BAC77355.1. AK000248 mRNA. Translation: BAA91029.1. Sequence problems. AK026371 mRNA. Translation: BAB15464.1. Different initiation. BC048345 mRNA. Translation: AAH48345.1. BC064981 mRNA. Translation: AAH64981.1.
IPI	IPI00302647. IPI00743836. IPI00759686.
RefSeq	NP_060191.3. NM_017721.4.
UniGene	Hs.269592.
3D structure databases
ProteinModelPortal	Q6P1N0.
SMR	Q6P1N0. Positions 647-776.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000313601.
PTM databases
PhosphoSite	Q6P1N0.
Polymorphism databases
DMDM	74737148.
Proteomic databases
PaxDb	Q6P1N0.
PRIDE	Q6P1N0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000318003; ENSP00000313601; ENSG00000132024. ENST00000589606; ENSP00000467526; ENSG00000132024.
GeneID	54862.
KEGG	hsa:54862.
UCSC	uc002mxo.2. human. uc002mxp.2. human.
Organism-specific databases
CTD	54862.
GeneCards	GC19P014016.
HGNC	HGNC:30237. CC2D1A.
HPA	CAB015220. HPA005436.
MIM	608443. phenotype. 610055. gene.
neXtProt	NX_Q6P1N0.
Orphanet	88616. Autosomal recessive nonsyndromic intellectual deficit.
PharmGKB	PA142672197.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG297234.
HOGENOM	HOG000285993.
HOVERGEN	HBG100866.
InParanoid	Q6P1N0.
OMA	MHKRKGP.
PhylomeDB	Q6P1N0.
Gene expression databases
Bgee	Q6P1N0.
CleanEx	HS_CC2D1A.
Genevestigator	Q6P1N0.
GermOnline	ENSG00000132024. Homo sapiens.
Family and domain databases
InterPro	IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR006608. DM14. [Graphical view]
Pfam	PF00168. C2. 1 hit. [Graphical view]
SMART	SM00239. C2. 1 hit. SM00685. DM14. 4 hits. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 1 hit.
PROSITE	PS50004. C2. False negative. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	CC2D1A. human.
GenomeRNAi	54862.
NextBio	57750.
SOURCE	Search...

Entry information

Entry name

C2D1A_HUMAN

Accession

Primary (citable) accession number: Q6P1N0
Secondary accession number(s): Q7Z435 , Q86XV0, Q8NF89, Q9H603, Q9NXI1

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 13, 2006
Last sequence update:	July 5, 2004
Last modified:	May 1, 2013
This is version 86 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.