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UniProtKB - Q86YS7 (C2CD5_HUMAN)

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Protein

C2 domain-containing protein 5

Gene

C2CD5

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

Functioni

Required for insulin-stimulated glucose transport and glucose transporter SLC2A4/GLUT4 translocation from intracellular glucose storage vesicle (GSV) to the plasma membrane (PM) in adipocytes. Binds phospholipid membranes in a calcium-dependent manner and is necessary for the optimal membrane fusion between SLC2A4/GLUT4 GSV and the PM.1 Publication

Cofactori

Ca2+Note: Binds 2 calcium ions per subunit. The ions are bound to the C2 domains.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi13 – 271; low affinityAdd BLAST15
Calcium bindingi75 – 862; high affinityAdd BLAST12

GO - Molecular functioni

  • calcium-dependent phospholipid binding Source: UniProtKB
  • calcium ion binding Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  • cellular response to insulin stimulus Source: UniProtKB
  • insulin receptor signaling pathway via phosphatidylinositol 3-kinase Source: UniProtKB
  • intracellular protein transmembrane transport Source: UniProtKB
  • positive regulation of glucose import in response to insulin stimulus Source: Ensembl
  • positive regulation of glucose transport Source: UniProtKB
  • positive regulation of protein targeting to membrane Source: UniProtKB
  • positive regulation of vesicle fusion Source: UniProtKB
  • protein localization to plasma membrane Source: Ensembl
  • vesicle fusion Source: Ensembl
Complete GO annotation...

Keywordsi

Biological processProtein transport, Transport
LigandCalcium, Lipid-binding

Enzyme and pathway databases

ReactomeiR-HSA-1445148. Translocation of GLUT4 to the plasma membrane.

Names & Taxonomyi

Protein namesi
Recommended name:
C2 domain-containing protein 5
Alternative name(s):
C2 domain-containing phosphoprotein of 138 kDa
Gene namesi
Name:C2CD5
Synonyms:CDP138, KIAA0528
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:29062. C2CD5.

Subcellular locationi

GO - Cellular componenti

  • cell cortex Source: UniProtKB
  • cytoplasmic vesicle membrane Source: UniProtKB
  • cytosol Source: HPA
  • microtubule organizing center Source: HPA
  • plasma membrane Source: UniProtKB
  • ruffle membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Cytoplasmic vesicle, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi19D → A: Reduces calcium-binding, phospholipid membrane-binding and insulin-stimulated SLC2A4/GLUT4 translocation; when associated with A-26; A-76; A-78 and A-84. 1 Publication1
Mutagenesisi26D → A: Reduces calcium-binding, phospholipid membrane-binding and insulin-stimulated SLC2A4/GLUT4 translocation; when associated with A-19; A-76; A-78 and A-84. 1 Publication1
Mutagenesisi76D → A: Reduces calcium-binding, phospholipid membrane-binding and insulin-stimulated SLC2A4/GLUT4 translocation; when associated with A-19; A-26; A-78 and A-84. 1 Publication1
Mutagenesisi78D → A: Reduces calcium-binding, phospholipid membrane-binding and insulin-stimulated SLC2A4/GLUT4 translocation; when associated with A-19; A-26; A-76 and A-84. 1 Publication1
Mutagenesisi84D → A: Reduces calcium-binding, phospholipid membrane-binding and insulin-stimulated SLC2A4/GLUT4 translocation; when associated with A-19; A-26; A-76 and A-78. 1 Publication1
Mutagenesisi197S → A: Inhibits insulin-stimulated AKT2-induced phosphorylation, SLC2A4/GLUT4 translocation to the cell surface and GSV-PM fusion. 1 Publication1
Mutagenesisi200S → A: Does not inhibit insulin-stimulated SLC2A4/GLUT4 translocation. 1 Publication1

Organism-specific databases

DisGeNETi9847.
OpenTargetsiENSG00000111731.
PharmGKBiPA143485515.

Polymorphism and mutation databases

DMDMi74750574.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002474501 – 1000C2 domain-containing protein 5Add BLAST1000

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei197Phosphoserine; by PKB/AKT21 Publication1
Modified residuei200Phosphoserine1 Publication1
Modified residuei260PhosphoserineCombined sources1
Modified residuei293PhosphoserineCombined sources1
Modified residuei295PhosphoserineCombined sources1
Modified residuei304PhosphoserineBy similarity1
Modified residuei305PhosphoserineCombined sources1
Modified residuei306PhosphoserineBy similarity1
Modified residuei317PhosphothreonineCombined sources1
Modified residuei323PhosphoserineCombined sources1
Modified residuei601PhosphothreonineCombined sources1
Modified residuei643PhosphoserineCombined sources1
Modified residuei657PhosphoserineBy similarity1
Modified residuei659PhosphoserineCombined sources1
Modified residuei661PhosphoserineBy similarity1
Modified residuei662PhosphoserineCombined sources1
Modified residuei666PhosphothreonineCombined sources1
Modified residuei671PhosphoserineCombined sources1
Modified residuei807PhosphothreonineCombined sources1
Modified residuei817PhosphoserineBy similarity1
Modified residuei852PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on Ser-197 by active myristoylated kinase AKT2; insulin-stimulated phosphorylation by AKT2 regulates SLC2A4/GLUT4 translocation into the plasma membrane.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ86YS7.
MaxQBiQ86YS7.
PaxDbiQ86YS7.
PeptideAtlasiQ86YS7.
PRIDEiQ86YS7.

PTM databases

iPTMnetiQ86YS7.
PhosphoSitePlusiQ86YS7.

Expressioni

Gene expression databases

BgeeiENSG00000111731.
CleanExiHS_KIAA0528.
ExpressionAtlasiQ86YS7. baseline and differential.
GenevisibleiQ86YS7. HS.

Organism-specific databases

HPAiHPA046194.

Interactioni

Protein-protein interaction databases

BioGridi115182. 32 interactors.
IntActiQ86YS7. 20 interactors.
STRINGi9606.ENSP00000334229.

Structurei

3D structure databases

ProteinModelPortaliQ86YS7.
SMRiQ86YS7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 90C2PROSITE-ProRule annotationAdd BLAST90

Domaini

The C2 domain binds to calcium and membrane lipids.

Phylogenomic databases

eggNOGiKOG1031. Eukaryota.
ENOG410XQDE. LUCA.
GeneTreeiENSGT00390000000212.
HOGENOMiHOG000006746.
HOVERGENiHBG081824.
InParanoidiQ86YS7.
OMAiCANSTVG.
OrthoDBiEOG091G0FX6.
PhylomeDBiQ86YS7.
TreeFamiTF323431.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiView protein in InterPro
IPR000008. C2_dom.
PfamiView protein in Pfam
PF00168. C2. 1 hit.
SMARTiView protein in SMART
SM00239. C2. 1 hit.
SUPFAMiSSF49562. SSF49562. 1 hit.
PROSITEiView protein in PROSITE
PS50004. C2. 1 hit.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86YS7-1) [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
MPGKLKVKIV AGRHLPVMDR ASDLTDAFVE VKFGNTTFKT DVYLKSLNPQ 
        60         70         80         90        100
WNSEWFKFEV DDEDLQDEPL QITVLDHDTY SANDAIGKVY IDIDPLLYSE 
       110        120        130        140        150
AATVISGWFP IYDTIHGIRG EINVVVKVDL FNDLNRFRQS SCGVKFFCTT 
       160        170        180        190        200
SIPKCYRAVI IHGFVEELVV NEDPEYQWID RIRTPRASNE ARQRLISLMS 
       210        220        230        240        250
GELQRKIGLK VLEMRGNAVV GYLQCFDLEG ESGLVVRAIG TACTLDKLSS 
       260        270        280        290        300
PAAFLPACNS PSKEMKEIPF NEDPNPNTHS SGPSTPLKNQ TYSFSPSKSY 
       310        320        330        340        350
SRQSSSSDTD LSLTPKTGMG SGSAGKEGGP FKALLRQQTQ SALEQREFPF 
       360        370        380        390        400
FTLTAFPPGF LVHVGGVVSA RSVKLLDRIH NPDEPETRDA WWAEIRQEIK 
       410        420        430        440        450
SHAKALGCHA VVGYSESTSI CEEVCILSAS GTAAVLNPRF LQDGTVEGCL 
       460        470        480        490        500
EQRLEENLPT RCGFCHIPYD ELNMPFPAHL TYCYNCRKQK VPDVLFTTID 
       510        520        530        540        550
LPTDATVIGK GCLIQARLCR LKKKAQAEAN ATAISNLLPF MEYEVHTQLM 
       560        570        580        590        600
NKLKLKGMNA LFGLRIQITV GENMLMGLAS ATGVYLAALP TPGGIQIAGK 
       610        620        630        640        650
TPNDGSYEQH ISHMQKKIND TIAKNKELYE INPPEISEEI IGSPIPEPRQ 
       660        670        680        690        700
RSRLLRSQSE SSDEVTELDL SHGKKDAFVL EIDDTDAMED VHSLLTDVPP 
       710        720        730        740        750
PSGFYSCNTE IMPGINNWTS EIQMFTSVRV IRLSSLNLTN QALNKNFNDL 
       760        770        780        790        800
CENLLKSLYF KLRSMIPCCL CHVNFTVSLP EDELIQVTVT AVAITFDKNQ 
       810        820        830        840        850
ALQTTKTPVE KSLQRASTDN EELLQFPLEL CSDSLPSHPF PPAKAMTVEK 
       860        870        880        890        900
ASPVGDGNFR NRSAPPCANS TVGVVKMTPL SFIPGAKITK YLGIINMFFI 
       910        920        930        940        950
RETTSLREEG GVSGFLHAFI AEVFAMVRAH VAALGGNAVV SYIMKQCVFM 
       960        970        980        990       1000
ENPNKNQAQC LINVSGDAVV FVRESDLEVV SSQQPTTNCQ SSCTEGEVTT
Length:1,000
Mass (Da):110,447
Last modified:June 1, 2003 - v1
Checksum:i7C51961F54CBBACD
GO
Isoform 2 (identifier: Q86YS7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     268-316: IPFNEDPNPN...SDTDLSLTPK → SPLVHPPSHG...FSVSVPTLIY
     845-845: A → EHLESASSNSGIPAAQRATSVDYSSFADRCSSWIELIKLKAQTIRRGSIKTT

Note: No experimental confirmation available.
Show »
Length:1,042
Mass (Da):114,994
Checksum:i23C91754C1A61236
GO
Isoform 3 (identifier: Q86YS7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     845-845: A → EHLESASSNSGIPAAQRATSVDYSSFADRCSSWIELIKLKAQTIRRGSIKTT

Note: No experimental confirmation available.
Show »
Length:1,051
Mass (Da):116,027
Checksum:i2C4D059D41F01BE8
GO
Isoform 4 (identifier: Q86YS7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     268-316: IPFNEDPNPN...SDTDLSLTPK → SPLVHPPSHG...FSVSVPTLIY
     345-345: Q → QRGGSPHRFCRR
     845-845: A → EHLESASSNSGIPAAQRATSVDYSSFADRCSSWIELIKLKAQTIRRGSIKTT

Note: No experimental confirmation available.Curated
Show »
Length:1,053
Mass (Da):116,305
Checksum:iF27416DC231838AA
GO
Isoform 5 (identifier: Q86YS7-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     268-316: IPFNEDPNPN...SDTDLSLTPK → SPLVHPPSHG...FSVSVPTLIY
     382-382: P → PAFVGIMGNTRSYKLLDWNSFNS
     845-845: A → EHLESASSNSGIPAAQRDRCSSWIELIKLKAQTIRRGSIKTT

Note: No experimental confirmation available.Curated
Show »
Length:1,054
Mass (Da):116,468
Checksum:i2514DE8DDDBDB3A7
GO

Sequence cautioni

The sequence BAA25454 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAG58665 differs from that shown. Reason: Frameshift at position 33.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti997E → G in BAG58665 (PubMed:14702039).Curated1
Isoform 4 (identifier: Q86YS7-4)
Sequence conflicti895I → F in AAI43879 (PubMed:15489334).Curated1
Isoform 5 (identifier: Q86YS7-5)
Sequence conflicti895S → P in BAG58665 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_028255268 – 316IPFNE…SLTPK → SPLVHPPSHGCRSTHNSPIH TATGSRLTQNFSVSVPTLIY in isoform 2, isoform 4 and isoform 5. 2 PublicationsAdd BLAST49
Alternative sequenceiVSP_055638345Q → QRGGSPHRFCRR in isoform 4. 1 Publication1
Alternative sequenceiVSP_055639382P → PAFVGIMGNTRSYKLLDWNS FNS in isoform 5. 1 Publication1
Alternative sequenceiVSP_028256845A → EHLESASSNSGIPAAQRATS VDYSSFADRCSSWIELIKLK AQTIRRGSIKTT in isoform 2, isoform 3 and isoform 4. 2 Publications1
Alternative sequenceiVSP_055640845A → EHLESASSNSGIPAAQRDRC SSWIELIKLKAQTIRRGSIK TT in isoform 5. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB011100 mRNA. Translation: BAA25454.3. Different initiation.
AY166851 mRNA. Translation: AAO17290.1.
AK295862 mRNA. Translation: BAG58665.1. Frameshift.
AK299353 mRNA. Translation: BAG61349.1.
AC053513 Genomic DNA. No translation available.
BC042498 mRNA. Translation: AAH42498.2.
BC053885 mRNA. Translation: AAH53885.1.
BC117143 mRNA. Translation: AAI17144.1.
BC143878 mRNA. Translation: AAI43879.1.
CCDSiCCDS31758.1. [Q86YS7-1]
CCDS66337.1. [Q86YS7-3]
CCDS66338.1. [Q86YS7-2]
CCDS66339.1. [Q86YS7-5]
CCDS66340.1. [Q86YS7-4]
PIRiT00072.
RefSeqiNP_001273102.1. NM_001286173.1. [Q86YS7-4]
NP_001273103.1. NM_001286174.1. [Q86YS7-3]
NP_001273104.1. NM_001286175.1. [Q86YS7-5]
NP_001273105.1. NM_001286176.1. [Q86YS7-3]
NP_001273106.1. NM_001286177.1. [Q86YS7-2]
NP_055617.1. NM_014802.2. [Q86YS7-1]
UniGeneiHs.271014.

Genome annotation databases

EnsembliENST00000333957; ENSP00000334229; ENSG00000111731. [Q86YS7-1]
ENST00000396028; ENSP00000379345; ENSG00000111731. [Q86YS7-2]
ENST00000446597; ENSP00000388756; ENSG00000111731. [Q86YS7-3]
ENST00000536386; ENSP00000439392; ENSG00000111731. [Q86YS7-4]
ENST00000542676; ENSP00000441951; ENSG00000111731. [Q86YS7-3]
ENST00000545552; ENSP00000443204; ENSG00000111731. [Q86YS7-5]
GeneIDi9847.
KEGGihsa:9847.
UCSCiuc001rfq.5. human. [Q86YS7-1]

Keywords - Coding sequence diversityi

Alternative splicing

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 nameiC2CD5_HUMAN
AccessioniPrimary (citable) accession number: Q86YS7
Secondary accession number(s): B4DJ03
, B4DRN7, B7ZLL0, F5H2A1, F5H5R1, O60280, Q17RY7, Q7Z619, Q86SU3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: June 1, 2003
Last modified: June 7, 2017
This is version 122 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 12
    Human chromosome 12: entries, gene names and cross-references to MIM