NECA2_MOUSE
ID NECA2_MOUSE Reviewed; 389 AA.
AC Q91ZP9; Q1LZI4; Q8C492;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=N-terminal EF-hand calcium-binding protein 2;
DE Short=EF-hand calcium-binding protein 2;
DE AltName: Full=Neuronal calcium-binding protein 2;
GN Name=Necab2; Synonyms=Efcbp2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RC STRAIN=NMRI; TISSUE=Embryo;
RX PubMed=11641222; DOI=10.1242/dev.128.20.3987;
RA Bernier G., Vukovich W., Neidhardt L., Herrmann B.G., Gruss P.;
RT "Isolation and characterization of a downstream target of Pax6 in the
RT mammalian retinal primordium.";
RL Development 128:3987-3994(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 19-389 (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [5]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-10 AND ARG-42, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [6]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=26843217; DOI=10.1007/s00429-016-1191-3;
RA Zhang M.D., Barde S., Szodorai E., Josephson A., Mitsios N., Watanabe M.,
RA Attems J., Lubec G., Kovacs G.G., Uhlen M., Mulder J., Harkany T.,
RA Hoekfelt T.;
RT "Comparative anatomical distribution of neuronal calcium-binding protein
RT (NECAB) 1 and -2 in rodent and human spinal cord.";
RL Brain Struct. Funct. 221:3803-3823(2016).
CC -!- FUNCTION: May act as a signaling scaffold protein that senses
CC intracellular calcium. Can modulate ligand-induced internalization of
CC ADORA2A and coupling efficiency of mGluR5/GRM5; for both receptors may
CC regulate signaling activity such as promoting MAPK1/3 (ERK1/2)
CC activation. {ECO:0000250|UniProtKB:Q7Z6G3}.
CC -!- SUBUNIT: Interacts (calcium-dependent) with ADORA2A and GRM5.
CC {ECO:0000250|UniProtKB:F1LQY6, ECO:0000250|UniProtKB:Q7Z6G3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11641222}. Cell
CC projection, dendrite {ECO:0000250|UniProtKB:F1LQY6}. Cell projection,
CC axon {ECO:0000250|UniProtKB:F1LQY6}. Cell membrane
CC {ECO:0000250|UniProtKB:Q7Z6G3}. Note=Colocalizes with ADORA2A and/or
CC mGluR5/GRM5 at the plasma membrane (By similarity). Found in neuronal
CC somata (PubMed:26843217). Detected in the cytoplasm of striatal
CC neurons, at postsynaptic sites, filling dendritic shafts and spines,
CC and at presynaptic sites, filling axon terminals (By similarity).
CC {ECO:0000250|UniProtKB:F1LQY6, ECO:0000250|UniProtKB:Q7Z6G3,
CC ECO:0000269|PubMed:26843217}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q91ZP9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q91ZP9-2; Sequence=VSP_024215;
CC -!- TISSUE SPECIFICITY: Expressed in the iris, in the ciliary margin of the
CC retina and in the inner portion of the neural retina. Expressed in the
CC spinal dorsal horn with especially strong expression in lamina IIi;
CC found in excitory synaptic boutons (at protein level).
CC {ECO:0000269|PubMed:11641222, ECO:0000269|PubMed:26843217}.
CC -!- DEVELOPMENTAL STAGE: Expressed in retina, retinal pigmented epithelium,
CC Rathke's pouch, corneal epithelium, the infundibulum and olfactory
CC placodes at 10.5 dpc (at protein level). Expressed in the inner region
CC of the neural retina, including the ganglion cell layer at 17.5 dpc (at
CC protein level). Expressed in the optic sulcus and in the pre-tectum at
CC 8.5 dpc. Expressed in the optic vesicle, in the midline position in the
CC roof of the midbrain and in the pre-tectum at 9.0-9.5 dpc. Expressed in
CC the olfactory placodes at 10.5 dpc. Expressed in retinal-pigmented
CC epithelium and in the neural retina, with strong expression in the
CC ciliary margin at 12.5-13.5 dpc. {ECO:0000269|PubMed:11641222}.
CC -!- INDUCTION: Up-regulated by PAX6. {ECO:0000269|PubMed:11641222}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC38589.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF411253; AAL04151.1; -; mRNA.
DR EMBL; BC115857; AAI15858.1; -; mRNA.
DR EMBL; BC115963; AAI15964.1; -; mRNA.
DR EMBL; AK082727; BAC38589.1; ALT_INIT; mRNA.
DR CCDS; CCDS22705.1; -. [Q91ZP9-1]
DR RefSeq; NP_473436.1; NM_054095.2. [Q91ZP9-1]
DR RefSeq; XP_017168015.1; XM_017312526.1. [Q91ZP9-2]
DR AlphaFoldDB; Q91ZP9; -.
DR SMR; Q91ZP9; -.
DR BioGRID; 228171; 8.
DR STRING; 10090.ENSMUSP00000095966; -.
DR iPTMnet; Q91ZP9; -.
DR PhosphoSitePlus; Q91ZP9; -.
DR MaxQB; Q91ZP9; -.
DR PaxDb; Q91ZP9; -.
DR PRIDE; Q91ZP9; -.
DR ProteomicsDB; 253053; -. [Q91ZP9-1]
DR ProteomicsDB; 253054; -. [Q91ZP9-2]
DR Antibodypedia; 2918; 115 antibodies from 22 providers.
DR DNASU; 117148; -.
DR Ensembl; ENSMUST00000098363; ENSMUSP00000095966; ENSMUSG00000031837. [Q91ZP9-1]
DR GeneID; 117148; -.
DR KEGG; mmu:117148; -.
DR UCSC; uc009npq.1; mouse. [Q91ZP9-1]
DR CTD; 54550; -.
DR MGI; MGI:2152211; Necab2.
DR VEuPathDB; HostDB:ENSMUSG00000031837; -.
DR eggNOG; ENOG502QRUC; Eukaryota.
DR GeneTree; ENSGT00950000183131; -.
DR HOGENOM; CLU_041553_1_0_1; -.
DR InParanoid; Q91ZP9; -.
DR OMA; ARHYPSK; -.
DR OrthoDB; 924307at2759; -.
DR PhylomeDB; Q91ZP9; -.
DR TreeFam; TF331029; -.
DR BioGRID-ORCS; 117148; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Necab2; mouse.
DR PRO; PR:Q91ZP9; -.
DR Proteomes; UP000000589; Chromosome 8.
DR RNAct; Q91ZP9; protein.
DR Bgee; ENSMUSG00000031837; Expressed in habenula and 158 other tissues.
DR Genevisible; Q91ZP9; MM.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0031687; F:A2A adenosine receptor binding; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0031802; F:type 5 metabotropic glutamate receptor binding; ISO:MGI.
DR GO; GO:1904021; P:negative regulation of G protein-coupled receptor internalization; ISO:MGI.
DR GO; GO:0060168; P:positive regulation of adenosine receptor signaling pathway; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:1900451; P:positive regulation of glutamate receptor signaling pathway; ISO:MGI.
DR GO; GO:1905477; P:positive regulation of protein localization to membrane; ISO:MGI.
DR GO; GO:0042984; P:regulation of amyloid precursor protein biosynthetic process; IBA:GO_Central.
DR CDD; cd00051; EFh; 1.
DR InterPro; IPR007138; ABM_dom.
DR InterPro; IPR011008; Dimeric_a/b-barrel.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR039862; NECAB1/2/3.
DR PANTHER; PTHR12178; PTHR12178; 1.
DR Pfam; PF03992; ABM; 1.
DR Pfam; PF13833; EF-hand_8; 2.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF54909; SSF54909; 1.
DR PROSITE; PS51725; ABM; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cell membrane; Cell projection; Coiled coil;
KW Cytoplasm; Membrane; Metal-binding; Methylation; Reference proteome;
KW Repeat.
FT CHAIN 1..389
FT /note="N-terminal EF-hand calcium-binding protein 2"
FT /id="PRO_0000282614"
FT DOMAIN 63..98
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 99..132
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 289..377
FT /note="ABM"
FT COILED 173..198
FT /evidence="ECO:0000255"
FT BINDING 76
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 78
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 80
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 82
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 87
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 110
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 112
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 114
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 116
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 121
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 10
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 42
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT VAR_SEQ 1..129
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_024215"
SQ SEQUENCE 389 AA; 43441 MW; 493F29BAFFD864EA CRC64;
MCERAARLCR AGAHRLLREP PPQGRALGGL LRWVGARMGE PRAPLVPDIP SADPGPGPAA
SRGGTAVILD IFRRADKNDD GKLSLEEFQL FFADGVLNEK ELEGLFHTID SDNTNHVDTK
ELCDYFVEHM GDYEDVLASL ETLNHSVLKA MGYTKKVYEG GSNVDQFVTR FLLKETANQI
QSLLSSVESA VEAIEEQTSQ IRQDHCKPSH AVNESRYGGP TPPYIPNHKL VAPEPMKSLP
VATGEPKEDG LEGQISRLAE LIGRLESKTL SFDLQQRLSD EEGTNMHLQL VRQEMAVCPE
QLSEFLDSLR QYLRSTAEER NCFHVAAVRM ADGLTFVIYE FWETEEEWKR HLQSPVCKAF
RHVKVDTLSQ PEALSQISVP AAWCTSGRD
