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Protein

Cell division cycle and apoptosis regulator protein 1

Gene

CCAR1

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

Functioni

Associates with components of the Mediator and p160 coactivator complexes that play a role as intermediaries transducing regulatory signals from upstream transcriptional activator proteins to basal transcription machinery at the core promoter. Recruited to endogenous nuclear receptor target genes in response to the appropriate hormone. Also functions as a p53 coactivator. May thus play an important role in transcriptional regulation (By similarity). May be involved in apoptosis signaling in the presence of the reinoid CD437. Apoptosis induction involves sequestration of 14-3-3 protein(s) and mediated altered expression of multiple cell cycle regulatory genes including MYC, CCNB1 and CDKN1A. Plays a role in cell cycle progression and/or cell proliferation (PubMed:12816952). In association with CALCOCO1 enhances GATA1- and MED1-mediated transcriptional activation from the gamma-globin promoter during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781). Can act as a both a coactivator and corepressor of AR-mediated transcription. Contributes to chromatin looping and AR transcription complex assembly by stabilizing AR-GATA2 association on chromatin and facilitating MED1 and RNA polymerase II recruitment to AR-binding sites. May play an important role in the growth and tumorigenesis of prostate cancer cells (PubMed:23887938).By similarity3 Publications

GO - Molecular functioni

  • core promoter binding Source: UniProtKB
  • ligand-dependent nuclear receptor transcription coactivator activity Source: MGI
  • poly(A) RNA binding Source: UniProtKB
  • transcription coactivator activity Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell cycle Source: UniProtKB-KW
  • mRNA splicing, via spliceosome Source: Reactome
  • positive regulation of cell migration Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Apoptosis, Cell cycle, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-72163. mRNA Splicing - Major Pathway.

Names & Taxonomyi

Protein namesi
Recommended name:
Cell division cycle and apoptosis regulator protein 1
Alternative name(s):
Cell cycle and apoptosis regulatory protein 1
Short name:
CARP-1
Death inducer with SAP domain
Gene namesi
Name:CCAR1
Synonyms:CARP1, DIS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:24236. CCAR1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi55749.
OpenTargetsiENSG00000060339.
PharmGKBiPA134920227.

Polymorphism and mutation databases

BioMutaiCCAR1.
DMDMi94707499.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002331481 – 1150Cell division cycle and apoptosis regulator protein 1Add BLAST1150

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei456PhosphoserineCombined sources1
Modified residuei627PhosphothreonineCombined sources1
Cross-linki637Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei667PhosphothreonineCombined sources1
Modified residuei685PhosphoserineCombined sources1
Modified residuei697PhosphoserineCombined sources1
Modified residuei861PhosphothreonineCombined sources1
Cross-linki1012Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki1012Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1067Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki1135Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ8IX12.
MaxQBiQ8IX12.
PaxDbiQ8IX12.
PeptideAtlasiQ8IX12.
PRIDEiQ8IX12.

PTM databases

iPTMnetiQ8IX12.
PhosphoSitePlusiQ8IX12.

Expressioni

Tissue specificityi

Expressed in various epithelial cancer cell lines, including breast, colon, prostate, pancreatic and leukemia. Expression is regulated by growth factors.1 Publication

Gene expression databases

BgeeiENSG00000060339.
CleanExiHS_CCAR1.
ExpressionAtlasiQ8IX12. baseline and differential.
GenevisibleiQ8IX12. HS.

Organism-specific databases

HPAiHPA007856.
HPA048513.

Interactioni

Subunit structurei

Directly interacts with ESR1, NR3C1 and p53/TP53 (By similarity). Interacts (via N-terminus) with CALCOCO1. Interacts with MED1 (By similarity). Interacts with GATA1. Interacts with AR and GATA2.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GOLGA2Q083793EBI-356265,EBI-618309
PIH1D3Q9NQM43EBI-356265,EBI-10239299
TRIM63Q969Q12EBI-356265,EBI-5661333
WWTR1Q9GZV52EBI-356265,EBI-747743
Wwtr1Q9EPK55EBI-356265,EBI-1211920From a different organism.

Protein-protein interaction databases

BioGridi120867. 52 interactors.
DIPiDIP-27607N.
IntActiQ8IX12. 37 interactors.
MINTiMINT-1139760.
STRINGi9606.ENSP00000265872.

Structurei

3D structure databases

ProteinModelPortaliQ8IX12.
SMRiQ8IX12.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini636 – 670SAPPROSITE-ProRule annotationAdd BLAST35

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 249Interaction with AR1 PublicationAdd BLAST249
Regioni203 – 660Interaction with GATA21 PublicationAdd BLAST458
Regioni643 – 1150Interaction with GATA11 PublicationAdd BLAST508

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili594 – 618Sequence analysisAdd BLAST25
Coiled coili1033 – 1114Sequence analysisAdd BLAST82

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi73 – 79Poly-Ala7
Compositional biasi293 – 361Arg-richAdd BLAST69
Compositional biasi673 – 889Glu-richAdd BLAST217

Sequence similaritiesi

Contains 1 SAP domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG4246. Eukaryota.
ENOG410Z0UJ. LUCA.
GeneTreeiENSGT00530000063672.
HOVERGENiHBG079908.
InParanoidiQ8IX12.
OMAiHPARLIK.
OrthoDBiEOG091G03QV.
PhylomeDBiQ8IX12.
TreeFamiTF316387.

Family and domain databases

Gene3Di1.10.720.30. 1 hit.
InterProiIPR025224. CCAR1/CCAR2.
IPR025954. DBC1/CARP1_inactive_NUDIX_dom.
IPR011992. EF-hand-dom_pair.
IPR012340. NA-bd_OB-fold.
IPR025223. S1-like_RNA-bd_dom.
IPR003034. SAP_dom.
[Graphical view]
PANTHERiPTHR14304. PTHR14304. 2 hits.
PfamiPF14443. DBC1. 1 hit.
PF14444. S1-like. 1 hit.
PF02037. SAP. 1 hit.
[Graphical view]
SMARTiSM01122. DBC1. 1 hit.
SM00513. SAP. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF50249. SSF50249. 1 hit.
PROSITEiPS50800. SAP. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q8IX12-1) [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
MAQFGGQKNP PWATQFTATA VSQPAALGVQ QPSLLGASPT IYTQQTALAA
60 70 80 90 100
AGLTTQTPAN YQLTQTAALQ QQAAAAAAAL QQQYSQPQQA LYSVQQQLQQ
110 120 130 140 150
PQQTLLTQPA VALPTSLSLS TPQPTAQITV SYPTPRSSQQ QTQPQKQRVF
160 170 180 190 200
TGVVTKLHDT FGFVDEDVFF QLSAVKGKTP QVGDRVLVEA TYNPNMPFKW
210 220 230 240 250
NAQRIQTLPN QNQSQTQPLL KTPPAVLQPI APQTTFGVQT QPQPQSLLQA
260 270 280 290 300
QISAASITPL LQTQPQPLLQ QPQQKAGLLQ PPVRIVSQPQ PARRLDPPSR
310 320 330 340 350
FSGRNDRGDQ VPNRKDDRSR ERERERRRSR ERSPQRKRSR ERSPRRERER
360 370 380 390 400
SPRRVRRVVP RYTVQFSKFS LDCPSCDMME LRRRYQNLYI PSDFFDAQFT
410 420 430 440 450
WVDAFPLSRP FQLGNYCNFY VMHREVESLE KNMAILDPPD ADHLYSAKVM
460 470 480 490 500
LMASPSMEDL YHKSCALAED PQELRDGFQH PARLVKFLVG MKGKDEAMAI
510 520 530 540 550
GGHWSPSLDG PDPEKDPSVL IKTAIRCCKA LTGIDLSVCT QWYRFAEIRY
560 570 580 590 600
HRPEETHKGR TVPAHVETVV LFFPDVWHCL PTRSEWETLS RGYKQQLVEK
610 620 630 640 650
LQGERKEADG EQDEEEKDDG EAKEISTPTH WSKLDPKTMK VNDLRKELES
660 670 680 690 700
RALSSKGLKS QLIARLTKQL KVEEQKEEQK ELEKSEKEED EDDDRKSEDD
710 720 730 740 750
KEEEERKRQE EIERQRRERR YILPDEPAII VHPNWAAKSG KFDCSIMSLS
760 770 780 790 800
VLLDYRLEDN KEHSFEVSLF AELFNEMLQR DFGVRIYKSL LSLPEKEDKK
810 820 830 840 850
EKDKKSKKDE RKDKKEERDD ETDEPKPKRR KSGDDKDKKE DRDERKKEDK
860 870 880 890 900
RKDDSKDDDE TEEDNNQDEY DPMEAEEAED EEDDRDEEEM TKRDDKRDIN
910 920 930 940 950
RYCKERPSKD KEKEKTQMIT INRDLLMAFV YFDQSHCGYL LEKDLEEILY
960 970 980 990 1000
TLGLHLSRAQ VKKLLNKVVL RESCFYRKLT DTSKDEENHE ESESLQEDML
1010 1020 1030 1040 1050
GNRLLLPTPT VKQESKDVEE NVGLIVYNGA MVDVGSLLQK LEKSEKVRAE
1060 1070 1080 1090 1100
VEQKLQLLEE KTDEDEKTIL NLENSNKSLS GELREVKKDL SQLQENLKIS
1110 1120 1130 1140 1150
ENMNLQFENQ MNKTIRNLST VMDEIHTVLK KDNVKNEDKD QKSKENGASV
Length:1,150
Mass (Da):132,821
Last modified:May 2, 2006 - v2
Checksum:i30618DCC8097F552
GO
Isoform 2 (identifier: Q8IX12-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     83-97: Missing.

Note: No experimental confirmation available.
Show »
Length:1,135
Mass (Da):131,043
Checksum:i1F36D655EC82941E
GO

Sequence cautioni

The sequence AAH26036 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
The sequence AAI08683 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
The sequence BAA91354 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti296D → Y in BAA91354 (PubMed:14702039).Curated1
Sequence conflicti305N → S in BAG60310 (PubMed:14702039).Curated1
Sequence conflicti492K → E in BAA91847 (PubMed:14702039).Curated1
Sequence conflicti618D → Y in AAH15475 (PubMed:15489334).Curated1
Sequence conflicti650S → G in AAO17319 (Ref. 2) Curated1
Sequence conflicti650S → G in BAA91700 (PubMed:14702039).Curated1
Sequence conflicti723L → S in BAF85338 (PubMed:14702039).Curated1
Sequence conflicti801 – 803EKD → KKK in AAH89420 (PubMed:15489334).Curated3
Sequence conflicti816 – 818EER → KKK in AAH15475 (PubMed:15489334).Curated3
Sequence conflicti853D → G (PubMed:12816952).Curated1
Sequence conflicti853D → G (Ref. 2) Curated1
Sequence conflicti853D → G in BAA91700 (PubMed:14702039).Curated1
Sequence conflicti1104N → S (PubMed:12816952).Curated1
Sequence conflicti1104N → S (Ref. 2) Curated1
Sequence conflicti1104N → S in BAA91700 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_058330588T → I.Corresponds to variant rs1782338dbSNPEnsembl.1
Natural variantiVAR_035497607E → K in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_058331681E → G.Corresponds to variant rs1060145dbSNPEnsembl.1
Natural variantiVAR_058332747M → V.Corresponds to variant rs11542602dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03773683 – 97Missing in isoform 2. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY249140 mRNA. Translation: AAP82002.1.
AF465616 mRNA. Translation: AAO17319.1.
AK000741 mRNA. Translation: BAA91354.1. Different initiation.
AK001452 mRNA. Translation: BAA91700.1.
AK001701 mRNA. Translation: BAA91847.1.
AK023438 mRNA. Translation: BAB14574.1.
AK298004 mRNA. Translation: BAG60310.1.
AK299307 mRNA. Translation: BAG61320.1.
AK292649 mRNA. Translation: BAF85338.1.
AL513534, AL391539 Genomic DNA. Translation: CAH70221.1.
AL391539, AL513534 Genomic DNA. Translation: CAH73835.1.
CH471083 Genomic DNA. Translation: EAW54302.1.
BC015475 mRNA. Translation: AAH15475.1.
BC026036 mRNA. Translation: AAH26036.1. Sequence problems.
BC089420 mRNA. Translation: AAH89420.1.
BC130626 mRNA. Translation: AAI30627.1.
BC132725 mRNA. Translation: AAI32726.1.
BC108682 mRNA. Translation: AAI08683.1. Sequence problems.
CCDSiCCDS60547.1. [Q8IX12-2]
CCDS7282.1. [Q8IX12-1]
RefSeqiNP_001269888.1. NM_001282959.1. [Q8IX12-2]
NP_001269889.1. NM_001282960.1. [Q8IX12-2]
NP_060707.2. NM_018237.3. [Q8IX12-1]
UniGeneiHs.49853.

Genome annotation databases

EnsembliENST00000265872; ENSP00000265872; ENSG00000060339. [Q8IX12-1]
ENST00000543719; ENSP00000445254; ENSG00000060339. [Q8IX12-2]
GeneIDi55749.
KEGGihsa:55749.
UCSCiuc001joo.5. human. [Q8IX12-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY249140 mRNA. Translation: AAP82002.1.
AF465616 mRNA. Translation: AAO17319.1.
AK000741 mRNA. Translation: BAA91354.1. Different initiation.
AK001452 mRNA. Translation: BAA91700.1.
AK001701 mRNA. Translation: BAA91847.1.
AK023438 mRNA. Translation: BAB14574.1.
AK298004 mRNA. Translation: BAG60310.1.
AK299307 mRNA. Translation: BAG61320.1.
AK292649 mRNA. Translation: BAF85338.1.
AL513534, AL391539 Genomic DNA. Translation: CAH70221.1.
AL391539, AL513534 Genomic DNA. Translation: CAH73835.1.
CH471083 Genomic DNA. Translation: EAW54302.1.
BC015475 mRNA. Translation: AAH15475.1.
BC026036 mRNA. Translation: AAH26036.1. Sequence problems.
BC089420 mRNA. Translation: AAH89420.1.
BC130626 mRNA. Translation: AAI30627.1.
BC132725 mRNA. Translation: AAI32726.1.
BC108682 mRNA. Translation: AAI08683.1. Sequence problems.
CCDSiCCDS60547.1. [Q8IX12-2]
CCDS7282.1. [Q8IX12-1]
RefSeqiNP_001269888.1. NM_001282959.1. [Q8IX12-2]
NP_001269889.1. NM_001282960.1. [Q8IX12-2]
NP_060707.2. NM_018237.3. [Q8IX12-1]
UniGeneiHs.49853.

3D structure databases

ProteinModelPortaliQ8IX12.
SMRiQ8IX12.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120867. 52 interactors.
DIPiDIP-27607N.
IntActiQ8IX12. 37 interactors.
MINTiMINT-1139760.
STRINGi9606.ENSP00000265872.

PTM databases

iPTMnetiQ8IX12.
PhosphoSitePlusiQ8IX12.

Polymorphism and mutation databases

BioMutaiCCAR1.
DMDMi94707499.

Proteomic databases

EPDiQ8IX12.
MaxQBiQ8IX12.
PaxDbiQ8IX12.
PeptideAtlasiQ8IX12.
PRIDEiQ8IX12.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265872; ENSP00000265872; ENSG00000060339. [Q8IX12-1]
ENST00000543719; ENSP00000445254; ENSG00000060339. [Q8IX12-2]
GeneIDi55749.
KEGGihsa:55749.
UCSCiuc001joo.5. human. [Q8IX12-1]

Organism-specific databases

CTDi55749.
DisGeNETi55749.
GeneCardsiCCAR1.
HGNCiHGNC:24236. CCAR1.
HPAiHPA007856.
HPA048513.
MIMi612569. gene.
neXtProtiNX_Q8IX12.
OpenTargetsiENSG00000060339.
PharmGKBiPA134920227.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4246. Eukaryota.
ENOG410Z0UJ. LUCA.
GeneTreeiENSGT00530000063672.
HOVERGENiHBG079908.
InParanoidiQ8IX12.
OMAiHPARLIK.
OrthoDBiEOG091G03QV.
PhylomeDBiQ8IX12.
TreeFamiTF316387.

Enzyme and pathway databases

ReactomeiR-HSA-72163. mRNA Splicing - Major Pathway.

Miscellaneous databases

ChiTaRSiCCAR1. human.
GeneWikiiCCAR1.
GenomeRNAii55749.
PROiQ8IX12.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000060339.
CleanExiHS_CCAR1.
ExpressionAtlasiQ8IX12. baseline and differential.
GenevisibleiQ8IX12. HS.

Family and domain databases

Gene3Di1.10.720.30. 1 hit.
InterProiIPR025224. CCAR1/CCAR2.
IPR025954. DBC1/CARP1_inactive_NUDIX_dom.
IPR011992. EF-hand-dom_pair.
IPR012340. NA-bd_OB-fold.
IPR025223. S1-like_RNA-bd_dom.
IPR003034. SAP_dom.
[Graphical view]
PANTHERiPTHR14304. PTHR14304. 2 hits.
PfamiPF14443. DBC1. 1 hit.
PF14444. S1-like. 1 hit.
PF02037. SAP. 1 hit.
[Graphical view]
SMARTiSM01122. DBC1. 1 hit.
SM00513. SAP. 1 hit.
[Graphical view]
SUPFAMiSSF47473. SSF47473. 1 hit.
SSF50249. SSF50249. 1 hit.
PROSITEiPS50800. SAP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCCAR1_HUMAN
AccessioniPrimary (citable) accession number: Q8IX12
Secondary accession number(s): A0JLT7
, A1L4P7, A8K9D4, B4DNP8, B4DRK8, Q32NE3, Q5EBM3, Q5VUP6, Q6PIZ0, Q6X935, Q9H8N4, Q9NVA7, Q9NVQ0, Q9NWM6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2006
Last sequence update: May 2, 2006
Last modified: November 30, 2016
This is version 124 of the entry and version 2 of the sequence. [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 10
    Human chromosome 10: 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
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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.