NECA2_RAT
ID NECA2_RAT Reviewed; 389 AA.
AC F1LQY6; Q9ESB4;
DT 05-JUL-2017, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2017, sequence version 3.
DT 03-AUG-2022, entry version 70.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway {ECO:0000312|EMBL:EDL92668.1};
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 18-389.
RX PubMed=12044471; DOI=10.1016/s0306-4522(02)00063-5;
RA Sugita S., Ho A., Suedhof T.C.;
RT "NECABs: a family of neuronal Ca(2+)-binding proteins with an unusual
RT domain structure and a restricted expression pattern.";
RL Neuroscience 112:51-63(2002).
RN [4]
RP INTERACTION WITH ADORA2A, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=17689978; DOI=10.1016/j.mcn.2007.05.007;
RA Canela L., Lujan R., Lluis C., Burgueno J., Mallol J., Canela E.I.,
RA Franco R., Ciruela F.;
RT "The neuronal Ca(2+) -binding protein 2 (NECAB2) interacts with the
RT adenosine A(2A) receptor and modulates the cell surface expression and
RT function of the receptor.";
RL Mol. Cell. Neurosci. 36:1-12(2007).
RN [5]
RP INTERACTION WITH GRM5, AND TISSUE SPECIFICITY.
RX PubMed=19694902; DOI=10.1111/j.1471-4159.2009.06348.x;
RA Canela L., Fernandez-Duenas V., Albergaria C., Watanabe M., Lluis C.,
RA Mallol J., Canela E.I., Franco R., Lujan R., Ciruela F.;
RT "The association of metabotropic glutamate receptor type 5 with the
RT neuronal Ca2+-binding protein 2 modulates receptor function.";
RL J. Neurochem. 111:555-567(2009).
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:0000269|PubMed:17689978, ECO:0000269|PubMed:19694902}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17689978}. Cell
CC projection, dendrite {ECO:0000269|PubMed:17689978}. Cell projection,
CC axon {ECO:0000269|PubMed:17689978}. 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 (PubMed:17689978).
CC {ECO:0000250|UniProtKB:Q7Z6G3, ECO:0000269|PubMed:17689978,
CC ECO:0000269|PubMed:26843217}.
CC -!- TISSUE SPECIFICITY: Expressed in the striatum; predominantly in the
CC caudate putamen. Expressed in hippocampus; particularly strong in the
CC CA1 area. Expressed in the spinal dorsal horn with especially strong
CC expression in lamina IIi; found in excitory synaptic boutons (at
CC protein level). {ECO:0000269|PubMed:17689978,
CC ECO:0000269|PubMed:19694902, ECO:0000269|PubMed:26843217}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG28413.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=EDL92668.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AABR07044001; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR07044002; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473972; EDL92668.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF193757; AAG28413.1; ALT_INIT; mRNA.
DR RefSeq; NP_596906.1; NM_133415.1.
DR AlphaFoldDB; F1LQY6; -.
DR SMR; F1LQY6; -.
DR IntAct; F1LQY6; 2.
DR STRING; 10116.ENSRNOP00000020341; -.
DR PaxDb; F1LQY6; -.
DR Ensembl; ENSRNOT00000020341; ENSRNOP00000020341; ENSRNOG00000015084.
DR GeneID; 170928; -.
DR KEGG; rno:170928; -.
DR CTD; 54550; -.
DR RGD; 621844; Necab2.
DR eggNOG; ENOG502QRUC; Eukaryota.
DR GeneTree; ENSGT00950000183131; -.
DR HOGENOM; CLU_041553_0_0_1; -.
DR InParanoid; F1LQY6; -.
DR OrthoDB; 924307at2759; -.
DR TreeFam; TF331029; -.
DR PRO; PR:F1LQY6; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Proteomes; UP000234681; Chromosome 19.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0031687; F:A2A adenosine receptor binding; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0031802; F:type 5 metabotropic glutamate receptor binding; ISO:RGD.
DR GO; GO:0019722; P:calcium-mediated signaling; NAS:RGD.
DR GO; GO:1904021; P:negative regulation of G protein-coupled receptor internalization; ISO:RGD.
DR GO; GO:0060168; P:positive regulation of adenosine receptor signaling pathway; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:1900451; P:positive regulation of glutamate receptor signaling pathway; ISO:RGD.
DR GO; GO:1905477; P:positive regulation of protein localization to membrane; ISO:RGD.
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 Calcium; Cell membrane; Cell projection; Coiled coil; Cytoplasm; Membrane;
KW Metal-binding; Methylation; Reference proteome; Repeat.
FT CHAIN 1..389
FT /note="N-terminal EF-hand calcium-binding protein 2"
FT /id="PRO_0000440700"
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:0000250|UniProtKB:Q91ZP9"
FT MOD_RES 42
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q91ZP9"
FT CONFLICT 205
FT /note="H -> Y (in Ref. 3; AAG28413)"
FT /evidence="ECO:0000305"
FT CONFLICT 210
FT /note="P -> H (in Ref. 3; AAG28413)"
FT /evidence="ECO:0000305"
FT CONFLICT 320
FT /note="R -> K (in Ref. 3; AAG28413)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="R -> K (in Ref. 3; AAG28413)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="A -> G (in Ref. 3; AAG28413)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 389 AA; 43526 MW; F517709A86144310 CRC64;
MCERAARLCR AGAHRLLREP PPQGRALGGL LRWVGARMGE PRAPLVPDIP AADPDPGPAA
PRGGTAVILD IFRRADKNDD GKLSLEEFQL FFADGVLNEK ELEGLFHTID SDNTNHVDTK
ELCDYFVEHM GDYEDVLASL ETLNHSVLKA MGYTKKVYEG GNNVDQFVTR FLLKETANQI
QSLLSSVESA VEAIEEQTSQ IRQDHCKPSP GVNESRYGGP TPPYIPNHKL VVPEPVKSLP
VAIGEPKEEG LEVQISRLAE LIGRLESKTL SFDLQQRLSD EEGTNMYLQL VRQEMAVCPE
QLGEFLDSLR QYLRSTAEER NCFHVAAVRM ADGLTFVIYE FWETEEEWKR HLQSPVCKAF
RHVKVDTLSQ PEALSQISVP AAWCTSGRD
