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Protein

N-terminal EF-hand calcium-binding protein 2

Gene

NECAB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

May act as a signaling scaffold protein that senses intracellular calcium. Can modulate ligand-induced internalization of ADORA2A and coupling efficiency of mGluR5/GRM5; for both receptors may regulate signaling activity such as promoting MAPK1/3 (ERK1/2) activation.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi73 – 841PROSITE-ProRule annotationAdd BLAST12
Calcium bindingi107 – 1182PROSITE-ProRule annotationAdd BLAST12

GO - Molecular functioni

  • A2A adenosine receptor binding Source: UniProtKB
  • calcium ion binding Source: InterPro
  • identical protein binding Source: IntAct
  • type 5 metabotropic glutamate receptor binding Source: UniProtKB

GO - Biological processi

  • negative regulation of G-protein coupled receptor internalization Source: UniProtKB
  • positive regulation of adenosine receptor signaling pathway Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of glutamate receptor signaling pathway Source: UniProtKB
  • positive regulation of protein localization to membrane Source: UniProtKB

Keywordsi

LigandCalcium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
N-terminal EF-hand calcium-binding protein 2
Short name:
EF-hand calcium-binding protein 2
Alternative name(s):
Neuronal calcium-binding protein 2
Synaptotagmin-interacting protein 2
Short name:
Stip-2
Gene namesi
Name:NECAB2
Synonyms:EFCBP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000103154.9.
HGNCiHGNC:23746. NECAB2.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi54550.
OpenTargetsiENSG00000103154.
PharmGKBiPA162397412.

Polymorphism and mutation databases

BioMutaiNECAB2.
DMDMi74762441.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002826131 – 386N-terminal EF-hand calcium-binding protein 2Add BLAST386

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10Omega-N-methylarginineBy similarity1
Modified residuei42Asymmetric dimethylarginineBy similarity1

Keywords - PTMi

Methylation

Proteomic databases

EPDiQ7Z6G3.
PaxDbiQ7Z6G3.
PeptideAtlasiQ7Z6G3.
PRIDEiQ7Z6G3.

PTM databases

PhosphoSitePlusiQ7Z6G3.

Expressioni

Tissue specificityi

Expressed in brain. Expressed in the spinal dorsal horn with especially strong expression in lamina IIi; found in excitory synaptic boutons and in ependymal cells (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000103154.
CleanExiHS_NECAB2.
ExpressionAtlasiQ7Z6G3. baseline and differential.
GenevisibleiQ7Z6G3. HS.

Organism-specific databases

HPAiCAB068211.
HPA013998.
HPA014144.

Interactioni

Subunit structurei

Interacts (calcium-dependent) with ADORA2A and GRM5.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ADORA2AP292746EBI-950070,EBI-2902702
AIMP2Q131553EBI-10172876,EBI-745226
BEX2Q9BXY83EBI-10172876,EBI-745073
BEX3Q009943EBI-10172876,EBI-741753
BYSLQ138953EBI-10172876,EBI-358049
C1orf109Q9NX043EBI-10172876,EBI-8643161
CAF40P538293EBI-10172876,EBI-28306From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
CARD9Q9H2573EBI-10172876,EBI-751319
CCDC146Q8IYE0-23EBI-10172876,EBI-10247802
CCDC151A5D8V73EBI-10172876,EBI-8466445
CCDC151A5D8V7-23EBI-10172876,EBI-10173824
CCDC153Q494R43EBI-10172876,EBI-10241443
CENPOQ9BU643EBI-10172876,EBI-745954
DAD4P698513EBI-10172876,EBI-975389From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
DAXXQ9UER73EBI-10172876,EBI-77321
DTNBP1Q96EV84EBI-950070,EBI-465804
EHHADHQ084263EBI-10172876,EBI-2339219
EIF4E2O605733EBI-10172876,EBI-398610
FAM161AQ3B8203EBI-10172876,EBI-719941
FAM161BQ96MY74EBI-950070,EBI-7225287
GCC1Q96CN93EBI-10172876,EBI-746252
GCD7P325023EBI-10172876,EBI-6260From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
GRM5P41594-12EBI-950070,EBI-14039683
HAUS1Q96CS23EBI-10172876,EBI-2514791
ISCUQ9H1K13EBI-10172876,EBI-1047335
KANSL1Q7Z3B33EBI-10172876,EBI-740244
KIFC3Q9BVG83EBI-10172876,EBI-2125614
KLC3Q6P5973EBI-10172876,EBI-1643885
KLC4Q9NSK03EBI-10172876,EBI-949319
KPNA2P522923EBI-10172876,EBI-349938
LENG1Q96BZ83EBI-10172876,EBI-726510
LNX1Q8TBB13EBI-10172876,EBI-739832
MRP4P329024EBI-10172876,EBI-16248From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
MRPS27Q92552-23EBI-10172876,EBI-10278573
NECAB1Q8N9874EBI-950070,EBI-11956853
NEK6Q9HC983EBI-10172876,EBI-740364
NIP7Q9Y2213EBI-10172876,EBI-749003
NUP57P488373EBI-10172876,EBI-12324From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
OIP5O434824EBI-950070,EBI-536879
PICK1Q9NRD54EBI-950070,EBI-79165
PRE5P403023EBI-10172876,EBI-13955From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
PRKAA2P546463EBI-10172876,EBI-1383852
PRPF18Q996334EBI-950070,EBI-2798416
RCOR3Q9P2K33EBI-10172876,EBI-743428
RIC8AQ9NPQ8-43EBI-10172876,EBI-9091816
RPC11Q043073EBI-10172876,EBI-15858From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
RUNX1T1Q06455-43EBI-10172876,EBI-10224192
SDCBPO005605EBI-10172876,EBI-727004
SH2D4AQ9H7883EBI-10172876,EBI-747035
SH2D4AQ9H788-23EBI-10172876,EBI-10308083
SRP1Q028213EBI-10172876,EBI-1797From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
SSC5DA1L4H13EBI-10172876,EBI-10172867
TAE1P383403EBI-10172876,EBI-21116From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
THP2O135393EBI-10172876,EBI-30898From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).
TTC25Q96NG33EBI-10172876,EBI-1046387
TTRP027663EBI-10172876,EBI-711909
USHBP1Q8N6Y03EBI-950070,EBI-739895
WDYHV1Q96HA85EBI-10172876,EBI-741158
YPL077CQ028313EBI-10172876,EBI-31828From Saccharomyces cerevisiae (strain ATCC 204508 / S288c).

GO - Molecular functioni

  • A2A adenosine receptor binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • type 5 metabotropic glutamate receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120035. 64 interactors.
IntActiQ7Z6G3. 90 interactors.
MINTiMINT-1442144.

Structurei

3D structure databases

ProteinModelPortaliQ7Z6G3.
SMRiQ7Z6G3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini60 – 95EF-hand 1PROSITE-ProRule annotationAdd BLAST36
Domaini94 – 129EF-hand 2PROSITE-ProRule annotationAdd BLAST36
Domaini286 – 375ABMAdd BLAST90

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili170 – 201Sequence analysisAdd BLAST32

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiENOG410IH3U. Eukaryota.
ENOG4111GJU. LUCA.
GeneTreeiENSGT00390000009734.
HOGENOMiHOG000008120.
HOVERGENiHBG050433.
InParanoidiQ7Z6G3.
OMAiWETEEAW.
OrthoDBiEOG091G0DWL.
PhylomeDBiQ7Z6G3.
TreeFamiTF331029.

Family and domain databases

CDDicd00051. EFh. 1 hit.
InterProiView protein in InterPro
IPR007138. ABM_dom.
IPR011008. Dimeric_a/b-barrel.
IPR011992. EF-hand-dom_pair.
IPR018247. EF_Hand_1_Ca_BS.
IPR002048. EF_hand_dom.
PfamiView protein in Pfam
PF03992. ABM. 1 hit.
PF13202. EF-hand_5. 1 hit.
PF13833. EF-hand_8. 1 hit.
SMARTiView protein in SMART
SM00054. EFh. 2 hits.
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF54909. SSF54909. 1 hit.
PROSITEiView protein in PROSITE
PS51725. ABM. 1 hit.
PS00018. EF_HAND_1. 2 hits.
PS50222. EF_HAND_2. 2 hits.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7Z6G3-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MCERAARLCR AGAHRLLREP PQQGRALGGL LRWVGARMGE PRESLAPAAP
60 70 80 90 100
ADPGPASPRG GTAVILDIFR RADKNDDGKL SLEEFQLFFA DGVLNEKELE
110 120 130 140 150
DLFHTIDSDN TNHVDTKELC DYFVDHMGDY EDVLASLETL NHSVLKAMGY
160 170 180 190 200
TKKVYEGGSN VDQFVTRFLL KETANQIQSL LSSVESAVEA IEEQTSQLRQ
210 220 230 240 250
NHIKPSHSAA QTWCGSPTPA SAPNHKLMAM EQGKTLPSAT EDAKEEGLEA
260 270 280 290 300
QISRLAELIG RLESKALWFD LQQRLSDEDG TNMHLQLVRQ EMAVCPEQLS
310 320 330 340 350
EFLDSLRQYL RGTTGVRNCF HITAVRLSDG FTFVIYEFWE TEEAWKRHLQ
360 370 380
SPLCKAFRHV KVDTLSQPEA LSRILVPAAW CTVGRD
Length:386
Mass (Da):43,194
Last modified:October 1, 2003 - v1
Checksum:iD5F32B9AACF1A1C1
GO
Isoform 2 (identifier: Q7Z6G3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-121: MCERAARLCR...NHVDTKELCD → MMMGSCPWRN...FTRLTLTTPN

Show »
Length:303
Mass (Da):34,322
Checksum:i0D700F56055354EF
GO

Sequence cautioni

The sequence AAI31616 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC86948 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048639233G → S. Corresponds to variant dbSNP:rs2292323Ensembl.1
Natural variantiVAR_048640235T → S. Corresponds to variant dbSNP:rs2292324Ensembl.1
Natural variantiVAR_048641308Q → H. Corresponds to variant dbSNP:rs2292329Ensembl.1
Natural variantiVAR_048642353L → V. Corresponds to variant dbSNP:rs2271298Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0589361 – 121MCERA…KELCD → MMMGSCPWRNSSSSLQMASL MRKNWRISFTRLTLTTPN in isoform 2. Add BLAST121

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY299331 mRNA. Translation: AAP57260.1.
AK127376 mRNA. Translation: BAC86948.1. Different initiation.
AC040169 Genomic DNA. No translation available.
BC016979 mRNA. No translation available.
BC131615 mRNA. Translation: AAI31616.1. Different initiation.
AF193758 mRNA. Translation: AAG28414.1.
AF070637 mRNA. Translation: AAC25392.1.
CCDSiCCDS10940.1. [Q7Z6G3-1]
CCDS82019.1. [Q7Z6G3-2]
RefSeqiNP_001316678.1. NM_001329749.1. [Q7Z6G3-2]
NP_061938.2. NM_019065.2. [Q7Z6G3-1]
UniGeneiHs.140950.

Genome annotation databases

EnsembliENST00000305202; ENSP00000307449; ENSG00000103154. [Q7Z6G3-1]
ENST00000565691; ENSP00000457354; ENSG00000103154. [Q7Z6G3-2]
GeneIDi54550.
KEGGihsa:54550.
UCSCiuc002fhd.4. human. [Q7Z6G3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNECA2_HUMAN
AccessioniPrimary (citable) accession number: Q7Z6G3
Secondary accession number(s): A2RRG3
, H3BTW2, O75547, Q6ZSK0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: October 1, 2003
Last modified: September 27, 2017
This is version 121 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations