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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
  • 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

HGNCiHGNC:23746. NECAB2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB-SubCell
  • plasma membrane Source: UniProtKB

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
ADORA2AP292745EBI-950070,EBI-2902702

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi120035. 64 interactors.
IntActiQ7Z6G3. 11 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

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

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: July 5, 2017
This is version 119 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