NECA3_HUMAN
ID NECA3_HUMAN Reviewed; 396 AA.
AC Q96P71; A8K780; E1P5N2; Q5JWF5; Q5JWF6; Q5JWF7; Q86VV1; Q9H433; Q9H8G8;
AC Q9HBW7; Q9HCQ9;
DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2003, sequence version 2.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=N-terminal EF-hand calcium-binding protein 3;
DE AltName: Full=Amyloid-beta A4 protein-binding family A member 2-binding protein;
DE AltName: Full=Nek2-interacting protein 1;
DE AltName: Full=Neuronal calcium-binding protein 3;
DE AltName: Full=X11L-binding protein 51;
GN Name=NECAB3; Synonyms=APBA2BP, NIP1, SYTIP2, XB51;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH NEK2, SUBCELLULAR
RP LOCATION, AND PHOSPHORYLATION.
RC TISSUE=Liver;
RX PubMed=14697346; DOI=10.1016/j.yexcr.2003.09.025;
RA Yoo J.C., Chang J.R., Kim S.H., Jang S.K., Wolgemuth D.J., Kim K., Rhee K.;
RT "NIP1/XB51/NECAB3 is a potential substrate of Nek2, suggesting specific
RT roles of Nek2 in Golgi.";
RL Exp. Cell Res. 292:393-402(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Placenta, and Skeletal muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 65-396 (ISOFORM 2), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND INTERACTION WITH APBA2.
RC TISSUE=Brain;
RX PubMed=10833507; DOI=10.1074/jbc.c000302200;
RA Lee D.-S., Tomita S., Kirino Y., Suzuki T.;
RT "Regulation of X11L-dependent amyloid precursor protein metabolism by XB51,
RT a novel X11L-binding protein.";
RL J. Biol. Chem. 275:23134-23138(2000).
RN [8]
RP FUNCTION, INTERACTION WITH APBA3 AND HIF1AN, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF HIS-358.
RX PubMed=26948053; DOI=10.1038/srep22784;
RA Nakaoka H.J., Hara T., Yoshino S., Kanamori A., Matsui Y., Shimamura T.,
RA Sato H., Murakami Y., Seiki M., Sakamoto T.;
RT "NECAB3 promotes activation of hypoxia-inducible factor-1 during normoxia
RT and enhances tumourigenicity of cancer cells.";
RL Sci. Rep. 6:22784-22784(2016).
CC -!- FUNCTION: Inhibits the interaction of APBA2 with amyloid-beta precursor
CC protein (APP), and hence allows formation of amyloid-beta. May enhance
CC the activity of HIF1A and thus promote glycolysis under normoxic
CC conditions; the function requires its ABM domain and may implicate the
CC stabilization of the interaction between HIF1AN and APBA3.
CC {ECO:0000269|PubMed:10833507, ECO:0000269|PubMed:26948053}.
CC -!- SUBUNIT: Interacts with the N-terminal domain of APBA2. Interacts with
CC NEK2. Interacts with APBA3; APBA3 seems to mediate the interaction
CC between NECAB3 and HIF1AN. {ECO:0000269|PubMed:10833507,
CC ECO:0000269|PubMed:14697346, ECO:0000269|PubMed:26948053}.
CC -!- INTERACTION:
CC Q96P71; O96018: APBA3; NbExp=2; IntAct=EBI-5773009, EBI-6115839;
CC Q96P71-2; O96018: APBA3; NbExp=4; IntAct=EBI-15098952, EBI-6115839;
CC Q96P71-2; P21917: DRD4; NbExp=3; IntAct=EBI-15098952, EBI-8592297;
CC Q96P71-2; Q14114-3: LRP8; NbExp=3; IntAct=EBI-15098952, EBI-25832196;
CC -!- SUBCELLULAR LOCATION: Golgi apparatus {ECO:0000269|PubMed:10833507,
CC ECO:0000269|PubMed:14697346, ECO:0000269|PubMed:26948053}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist. Experimental confirmation
CC may be lacking for some isoforms.;
CC Name=2; Synonyms=XB51-alpha;
CC IsoId=Q96P71-1; Sequence=Displayed;
CC Name=1; Synonyms=XB51-beta;
CC IsoId=Q96P71-2; Sequence=VSP_000739;
CC Name=3;
CC IsoId=Q96P71-3; Sequence=VSP_000737, VSP_000738;
CC -!- TISSUE SPECIFICITY: Strongly expressed in heart and skeletal muscle,
CC moderately in brain and pancreas. {ECO:0000269|PubMed:10833507,
CC ECO:0000269|PubMed:12044471}.
CC -!- PTM: Phosphorylated by NEK2. {ECO:0000305|PubMed:14697346}.
CC -!- MISCELLANEOUS: [Isoform 3]: May result from the retention of an intron
CC in the cDNA. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB14649.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB16413.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF193759; AAG28415.1; -; mRNA.
DR EMBL; AF409141; AAL01118.1; -; mRNA.
DR EMBL; AK023706; BAB14649.1; ALT_FRAME; mRNA.
DR EMBL; AK291895; BAF84584.1; -; mRNA.
DR EMBL; AL121906; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76302.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76304.1; -; Genomic_DNA.
DR EMBL; BC047673; AAH47673.1; -; mRNA.
DR EMBL; AB039947; BAB16413.1; ALT_INIT; mRNA.
DR CCDS; CCDS42866.1; -. [Q96P71-1]
DR CCDS; CCDS42867.1; -. [Q96P71-2]
DR RefSeq; NP_112508.3; NM_031231.3. [Q96P71-2]
DR RefSeq; NP_112509.3; NM_031232.3. [Q96P71-1]
DR AlphaFoldDB; Q96P71; -.
DR SMR; Q96P71; -.
DR BioGRID; 122006; 10.
DR CORUM; Q96P71; -.
DR IntAct; Q96P71; 10.
DR MINT; Q96P71; -.
DR STRING; 9606.ENSP00000246190; -.
DR CarbonylDB; Q96P71; -.
DR iPTMnet; Q96P71; -.
DR PhosphoSitePlus; Q96P71; -.
DR BioMuta; NECAB3; -.
DR DMDM; 41688800; -.
DR jPOST; Q96P71; -.
DR MassIVE; Q96P71; -.
DR PaxDb; Q96P71; -.
DR PeptideAtlas; Q96P71; -.
DR PRIDE; Q96P71; -.
DR ProteomicsDB; 77645; -. [Q96P71-1]
DR ProteomicsDB; 77646; -. [Q96P71-2]
DR ProteomicsDB; 77647; -. [Q96P71-3]
DR Antibodypedia; 25664; 142 antibodies from 26 providers.
DR DNASU; 63941; -.
DR Ensembl; ENST00000246190.11; ENSP00000246190.6; ENSG00000125967.17. [Q96P71-1]
DR Ensembl; ENST00000375238.8; ENSP00000364386.4; ENSG00000125967.17. [Q96P71-2]
DR GeneID; 63941; -.
DR KEGG; hsa:63941; -.
DR MANE-Select; ENST00000246190.11; ENSP00000246190.6; NM_031232.4; NP_112509.3.
DR UCSC; uc002wzm.5; human. [Q96P71-1]
DR CTD; 63941; -.
DR DisGeNET; 63941; -.
DR GeneCards; NECAB3; -.
DR HGNC; HGNC:15851; NECAB3.
DR HPA; ENSG00000125967; Low tissue specificity.
DR MIM; 612478; gene.
DR neXtProt; NX_Q96P71; -.
DR OpenTargets; ENSG00000125967; -.
DR PharmGKB; PA24871; -.
DR VEuPathDB; HostDB:ENSG00000125967; -.
DR eggNOG; ENOG502QWRY; Eukaryota.
DR GeneTree; ENSGT00950000183131; -.
DR InParanoid; Q96P71; -.
DR OMA; EACFILY; -.
DR OrthoDB; 924307at2759; -.
DR PhylomeDB; Q96P71; -.
DR TreeFam; TF331029; -.
DR PathwayCommons; Q96P71; -.
DR SignaLink; Q96P71; -.
DR BioGRID-ORCS; 63941; 16 hits in 1080 CRISPR screens.
DR ChiTaRS; NECAB3; human.
DR GeneWiki; APBA2BP; -.
DR GenomeRNAi; 63941; -.
DR Pharos; Q96P71; Tbio.
DR PRO; PR:Q96P71; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q96P71; protein.
DR Bgee; ENSG00000125967; Expressed in right adrenal gland cortex and 192 other tissues.
DR ExpressionAtlas; Q96P71; baseline and differential.
DR Genevisible; Q96P71; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0000137; C:Golgi cis cisterna; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0019538; P:protein metabolic process; IDA:UniProtKB.
DR GO; GO:0009306; P:protein secretion; NAS:UniProtKB.
DR GO; GO:0042984; P:regulation of amyloid precursor protein biosynthetic process; IDA:UniProtKB.
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; PF13202; EF-hand_5; 1.
DR SMART; SM00054; EFh; 1.
DR SUPFAM; SSF47473; SSF47473; 1.
DR SUPFAM; SSF54909; SSF54909; 1.
DR PROSITE; PS51725; ABM; 1.
DR PROSITE; PS00018; EF_HAND_1; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Golgi apparatus; Metal-binding;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..396
FT /note="N-terminal EF-hand calcium-binding protein 3"
FT /id="PRO_0000073863"
FT DOMAIN 36..71
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 296..385
FT /note="ABM"
FT REGION 14..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 181..190
FT /note="Required for interaction with APBA3"
FT /evidence="ECO:0000269|PubMed:26948053"
FT REGION 197..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..31
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 199..220
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 49
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 51
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 53
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 55
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 60
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT VAR_SEQ 176..203
FT /note="SDAESVEAQSRLCGSRRAGRRALRSVSR -> YVRVLSTCGASAQAPIVPPF
FT QIPTVPAS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_000737"
FT VAR_SEQ 204..396
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_000738"
FT VAR_SEQ 242..275
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:12044471,
FT ECO:0000303|PubMed:14697346, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_000739"
FT VARIANT 254
FT /note="P -> L (in dbSNP:rs17124890)"
FT /id="VAR_048643"
FT MUTAGEN 358
FT /note="H->A: No effect on interaction with APBA3."
FT /evidence="ECO:0000269|PubMed:26948053"
FT CONFLICT 383
FT /note="T -> I (in Ref. 1; AAG28415)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 396 AA; 44350 MW; 9B24503AA629CB45 CRC64;
MACAGLLTVC LLRPPAPQPQ PQTPRHPQLA PDPGPAGHTL FQDVFRRADK NDDGKLSFEE
FQNYFADGVL SLGELQELFS GIDGHLTDNL ETEKLCDYFS EHLGVYRPVL AALESLNRAV
LAAMDATKLE YERASKVDQF VTRFLLRETV SQLQALQSSL EGASDTLEAQ AHGWRSDAES
VEAQSRLCGS RRAGRRALRS VSRSSTWSPG SSDTGRSSEA EMQWRLQVNR LQELIDQLEC
KVRAVGPGPH KGGPSWYPPE PGPCWRPGPH SVPSQAPRLE PLREEDLAKG PDLHILMAQR
QVQVAEEGLQ DFHRALRCYV DFTGAQSHCL HVSAQKMLDG ASFTLYEFWQ DEASWRRHQQ
SPGSKAFQRI LIDHLRAPDT LTTVFFPASW WIMNNN
