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Protein

Cullin-associated NEDD8-dissociated protein 1

Gene

CAND1

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

Functioni

Key assembly factor of SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complexes that promotes the exchange of the substrate-recognition F-box subunit in SCF complexes, thereby playing a key role in the cellular repertoire of SCF complexes. Acts as a F-box protein exchange factor. The exchange activity of CAND1 is coupled with cycles of neddylation conjugation: in the deneddylated state, cullin-binding CAND1 binds CUL1-RBX1, increasing dissociation of the SCF complex and promoting exchange of the F-box protein. Probably plays a similar role in other cullin-RING E3 ubiquitin ligase complexes.6 Publications

Miscellaneous

A model has been proposed to explain the mechanisms of cullin-RING E3 ubiquitin ligase complexes assembly. According to this hypothesis, cullin-RING E3 ubiquitin ligase complexes exist in a 'stable' active state when saturated with substrate, occluding access to deneddylation by the COP9 signalosome (CSN) complex. The neddylation-conjugated cullin-RING E3 ubiquitin ligase complexes mediate ubiquitination of substrates and can recruit downstream factors involved in substrate degradation. Depletion of the substrate promotes the ability of CSN to bind the cullin-RING E3 ubiquitin ligase complex and mediate deneddylation. In this 'intermediate' deneddylated state, the complex can bind CAND1 and enter the 'exchange' state, resulting in high increase in dissociation rate of the substrate-recognition subunit. The resulting CAND1-cullin-RING complex rapidly assembles with another available substrate-recognition subunit to form an unstable ternary intermediate and yield a new cullin-RING E3 ubiquitin ligase complex. Subsequent neddylation of the cullin, which is stabilized by substrate, completes the cycle (PubMed:23453757).1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-6798695 Neutrophil degranulation
R-HSA-8951664 Neddylation
R-HSA-917937 Iron uptake and transport

Names & Taxonomyi

Protein namesi
Recommended name:
Cullin-associated NEDD8-dissociated protein 1
Alternative name(s):
Cullin-associated and neddylation-dissociated protein 1
TBP-interacting protein of 120 kDa A
Short name:
TBP-interacting protein 120A
p120 CAND1
Gene namesi
Name:CAND1
Synonyms:KIAA0829, TIP120, TIP120A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000111530.12
HGNCiHGNC:30688 CAND1
MIMi607727 gene
neXtProtiNX_Q86VP6

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

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi55832
OpenTargetsiENSG00000111530
PharmGKBiPA142672207

Polymorphism and mutation databases

BioMutaiCAND1
DMDMi67460541

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources2 Publications
ChainiPRO_00000892932 – 1230Cullin-associated NEDD8-dissociated protein 1Add BLAST1229

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources2 Publications1
Modified residuei55N6-acetyllysineCombined sources1
Modified residuei335PhosphoserineCombined sources1
Modified residuei558PhosphoserineCombined sources1
Modified residuei971N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ86VP6
MaxQBiQ86VP6
PaxDbiQ86VP6
PeptideAtlasiQ86VP6
PRIDEiQ86VP6
ProteomicsDBi70051
70052 [Q86VP6-2]
70053 [Q86VP6-3]

PTM databases

iPTMnetiQ86VP6
PhosphoSitePlusiQ86VP6
SwissPalmiQ86VP6

Expressioni

Inductioni

Repressed by miR-148a.1 Publication

Gene expression databases

BgeeiENSG00000111530 Expressed in 231 organ(s), highest expression level in kidney
ExpressionAtlasiQ86VP6 baseline and differential
GenevisibleiQ86VP6 HS

Organism-specific databases

HPAiHPA055748
HPA062833
HPA069053

Interactioni

Subunit structurei

Interacts with TBP (By similarity). Part of a complex that contains CUL1 and RBX1. Interacts with unneddylated cullins: interacts with CUL1, CUL2, CUL3, CUL4A, CUL4B and CUL5. Does not bind neddylated CUL1. Interaction with cullins is abolished in presence of COMMD1, which antagonizes with CAND1 for interacting with cullins. Interacts with DCUN1D3.By similarity9 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120937, 708 interactors
CORUMiQ86VP6
DIPiDIP-31608N
IntActiQ86VP6, 34 interactors
MINTiQ86VP6
STRINGi9606.ENSP00000299218

Structurei

Secondary structure

11230
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ86VP6
SMRiQ86VP6
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ86VP6

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati2 – 39HEAT 1Add BLAST38
Repeati44 – 81HEAT 2Add BLAST38
Repeati83 – 119HEAT 3Add BLAST37
Repeati131 – 165HEAT 4Add BLAST35
Repeati171 – 208HEAT 5Add BLAST38
Repeati210 – 247HEAT 6Add BLAST38
Repeati248 – 282HEAT 7Add BLAST35
Repeati289 – 366HEAT 8Add BLAST78
Repeati370 – 407HEAT 9Add BLAST38
Repeati424 – 467HEAT 10Add BLAST44
Repeati471 – 510HEAT 11Add BLAST40
Repeati515 – 552HEAT 12Add BLAST38
Repeati563 – 602HEAT 13Add BLAST40
Repeati606 – 643HEAT 14Add BLAST38
Repeati646 – 683HEAT 15Add BLAST38
Repeati688 – 725HEAT 16Add BLAST38
Repeati729 – 768HEAT 17Add BLAST40
Repeati770 – 808HEAT 18Add BLAST39
Repeati809 – 845HEAT 19Add BLAST37
Repeati852 – 889HEAT 20Add BLAST38
Repeati890 – 927HEAT 21Add BLAST38
Repeati928 – 960HEAT 22Add BLAST33
Repeati961 – 998HEAT 23Add BLAST38
Repeati1002 – 1039HEAT 24Add BLAST38
Repeati1043 – 1097HEAT 25Add BLAST55
Repeati1099 – 1133HEAT 26Add BLAST35
Repeati1140 – 1189HEAT 27Add BLAST50

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi314 – 344Asp-richAdd BLAST31

Sequence similaritiesi

Belongs to the CAND family.Curated

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG1824 Eukaryota
ENOG410XPK4 LUCA
GeneTreeiENSGT00390000017740
HOVERGENiHBG053467
InParanoidiQ86VP6
KOiK17263
OMAiMASHQYH
OrthoDBiEOG091G017Q
PhylomeDBiQ86VP6
TreeFamiTF300355

Family and domain databases

Gene3Di1.25.10.10, 2 hits
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR013932 TATA-bd_TIP120
PfamiView protein in Pfam
PF08623 TIP120, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q86VP6-1) [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
MASASYHISN LLEKMTSSDK DFRFMATNDL MTELQKDSIK LDDDSERKVV
60 70 80 90 100
KMILKLLEDK NGEVQNLAVK CLGPLVSKVK EYQVETIVDT LCTNMLSDKE
110 120 130 140 150
QLRDISSIGL KTVIGELPPA SSGSALAANV CKKITGRLTS AIAKQEDVSV
160 170 180 190 200
QLEALDIMAD MLSRQGGLLV NFHPSILTCL LPQLTSPRLA VRKRTIIALG
210 220 230 240 250
HLVMSCGNIV FVDLIEHLLS ELSKNDSMST TRTYIQCIAA ISRQAGHRIG
260 270 280 290 300
EYLEKIIPLV VKFCNVDDDE LREYCIQAFE SFVRRCPKEV YPHVSTIINI
310 320 330 340 350
CLKYLTYDPN YNYDDEDEDE NAMDADGGDD DDQGSDDEYS DDDDMSWKVR
360 370 380 390 400
RAAAKCLDAV VSTRHEMLPE FYKTVSPALI SRFKEREENV KADVFHAYLS
410 420 430 440 450
LLKQTRPVQS WLCDPDAMEQ GETPLTMLQS QVPNIVKALH KQMKEKSVKT
460 470 480 490 500
RQCCFNMLTE LVNVLPGALT QHIPVLVPGI IFSLNDKSSS SNLKIDALSC
510 520 530 540 550
LYVILCNHSP QVFHPHVQAL VPPVVACVGD PFYKITSEAL LVTQQLVKVI
560 570 580 590 600
RPLDQPSSFD ATPYIKDLFT CTIKRLKAAD IDQEVKERAI SCMGQIICNL
610 620 630 640 650
GDNLGSDLPN TLQIFLERLK NEITRLTTVK ALTLIAGSPL KIDLRPVLGE
660 670 680 690 700
GVPILASFLR KNQRALKLGT LSALDILIKN YSDSLTAAMI DAVLDELPPL
710 720 730 740 750
ISESDMHVSQ MAISFLTTLA KVYPSSLSKI SGSILNELIG LVRSPLLQGG
760 770 780 790 800
ALSAMLDFFQ ALVVTGTNNL GYMDLLRMLT GPVYSQSTAL THKQSYYSIA
810 820 830 840 850
KCVAALTRAC PKEGPAVVGQ FIQDVKNSRS TDSIRLLALL SLGEVGHHID
860 870 880 890 900
LSGQLELKSV ILEAFSSPSE EVKSAASYAL GSISVGNLPE YLPFVLQEIT
910 920 930 940 950
SQPKRQYLLL HSLKEIISSA SVVGLKPYVE NIWALLLKHC ECAEEGTRNV
960 970 980 990 1000
VAECLGKLTL IDPETLLPRL KGYLISGSSY ARSSVVTAVK FTISDHPQPI
1010 1020 1030 1040 1050
DPLLKNCIGD FLKTLEDPDL NVRRVALVTF NSAAHNKPSL IRDLLDTVLP
1060 1070 1080 1090 1100
HLYNETKVRK ELIREVEMGP FKHTVDDGLD IRKAAFECMY TLLDSCLDRL
1110 1120 1130 1140 1150
DIFEFLNHVE DGLKDHYDIK MLTFLMLVRL STLCPSAVLQ RLDRLVEPLR
1160 1170 1180 1190 1200
ATCTTKVKAN SVKQEFEKQD ELKRSAMRAV AALLTIPEAE KSPLMSEFQS
1210 1220 1230
QISSNPELAA IFESIQKDSS STNLESMDTS
Length:1,230
Mass (Da):136,376
Last modified:June 7, 2005 - v2
Checksum:iFE344558F72D79D8
GO
Isoform 2 (identifier: Q86VP6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     458-625: Missing.

Note: No experimental confirmation available.
Show »
Length:1,062
Mass (Da):117,889
Checksum:i2045EBFCEE84468B
GO
Isoform 3 (identifier: Q86VP6-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-157: Missing.
     549-560: VIRPLDQPSSFD → AHHMPEAQWLRL
     561-1230: Missing.

Note: No experimental confirmation available.
Show »
Length:403
Mass (Da):45,539
Checksum:i4EC2B75A93D82663
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0C4DGH5A0A0C4DGH5_HUMAN
Cullin-associated NEDD8-dissociated...
CAND1
770Annotation score:
H0YH27H0YH27_HUMAN
Cullin-associated NEDD8-dissociated...
CAND1
442Annotation score:
F5H6I6F5H6I6_HUMAN
Cullin-associated NEDD8-dissociated...
CAND1
54Annotation score:

Sequence cautioni

The sequence BAA74852 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAB55090 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti272R → K in BAB55365 (PubMed:14702039).Curated1
Sequence conflicti457M → I in BAB55090 (PubMed:14702039).Curated1
Sequence conflicti606S → P in AAF67492 (PubMed:10931946).Curated1
Sequence conflicti609P → S in AAF67492 (PubMed:10931946).Curated1
Sequence conflicti1047T → S in AAF67492 (PubMed:10931946).Curated1
Sequence conflicti1177M → T in BAB55090 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_054041803V → A. Corresponds to variant dbSNP:rs12580996Ensembl.1
Natural variantiVAR_025327952A → V1 PublicationCorresponds to variant dbSNP:rs17854618Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0139471 – 157Missing in isoform 3. 1 PublicationAdd BLAST157
Alternative sequenceiVSP_013948458 – 625Missing in isoform 2. 1 PublicationAdd BLAST168
Alternative sequenceiVSP_013949549 – 560VIRPL…PSSFD → AHHMPEAQWLRL in isoform 3. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_013950561 – 1230Missing in isoform 3. 1 PublicationAdd BLAST670

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020636 mRNA Translation: BAA74852.2 Different initiation.
AF157326 mRNA Translation: AAF67492.1
AL133560 mRNA Translation: CAB63714.1
AL136810 mRNA Translation: CAB66744.1
AL833880 mRNA Translation: CAD38737.1
CH471054 Genomic DNA Translation: EAW97172.1
BC004232 mRNA Translation: AAH04232.1
BC026220 mRNA Translation: AAH26220.1
BC050341 mRNA Translation: AAH50341.1
AK027404 mRNA Translation: BAB55090.1 Different initiation.
AK027783 mRNA Translation: BAB55365.1
AK314358 mRNA Translation: BAG36990.1
CCDSiCCDS8977.1 [Q86VP6-1]
PIRiT43441
RefSeqiNP_060918.2, NM_018448.4 [Q86VP6-1]
UniGeneiHs.546407

Genome annotation databases

EnsembliENST00000545606; ENSP00000442318; ENSG00000111530 [Q86VP6-1]
GeneIDi55832
KEGGihsa:55832
UCSCiuc001stn.3 human [Q86VP6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB020636 mRNA Translation: BAA74852.2 Different initiation.
AF157326 mRNA Translation: AAF67492.1
AL133560 mRNA Translation: CAB63714.1
AL136810 mRNA Translation: CAB66744.1
AL833880 mRNA Translation: CAD38737.1
CH471054 Genomic DNA Translation: EAW97172.1
BC004232 mRNA Translation: AAH04232.1
BC026220 mRNA Translation: AAH26220.1
BC050341 mRNA Translation: AAH50341.1
AK027404 mRNA Translation: BAB55090.1 Different initiation.
AK027783 mRNA Translation: BAB55365.1
AK314358 mRNA Translation: BAG36990.1
CCDSiCCDS8977.1 [Q86VP6-1]
PIRiT43441
RefSeqiNP_060918.2, NM_018448.4 [Q86VP6-1]
UniGeneiHs.546407

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1U6GX-ray3.10C1-1230[»]
4A0CX-ray3.80A/B1-1230[»]
ProteinModelPortaliQ86VP6
SMRiQ86VP6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120937, 708 interactors
CORUMiQ86VP6
DIPiDIP-31608N
IntActiQ86VP6, 34 interactors
MINTiQ86VP6
STRINGi9606.ENSP00000299218

PTM databases

iPTMnetiQ86VP6
PhosphoSitePlusiQ86VP6
SwissPalmiQ86VP6

Polymorphism and mutation databases

BioMutaiCAND1
DMDMi67460541

Proteomic databases

EPDiQ86VP6
MaxQBiQ86VP6
PaxDbiQ86VP6
PeptideAtlasiQ86VP6
PRIDEiQ86VP6
ProteomicsDBi70051
70052 [Q86VP6-2]
70053 [Q86VP6-3]

Protocols and materials databases

DNASUi55832
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000545606; ENSP00000442318; ENSG00000111530 [Q86VP6-1]
GeneIDi55832
KEGGihsa:55832
UCSCiuc001stn.3 human [Q86VP6-1]

Organism-specific databases

CTDi55832
DisGeNETi55832
EuPathDBiHostDB:ENSG00000111530.12
GeneCardsiCAND1
HGNCiHGNC:30688 CAND1
HPAiHPA055748
HPA062833
HPA069053
MIMi607727 gene
neXtProtiNX_Q86VP6
OpenTargetsiENSG00000111530
PharmGKBiPA142672207
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1824 Eukaryota
ENOG410XPK4 LUCA
GeneTreeiENSGT00390000017740
HOVERGENiHBG053467
InParanoidiQ86VP6
KOiK17263
OMAiMASHQYH
OrthoDBiEOG091G017Q
PhylomeDBiQ86VP6
TreeFamiTF300355

Enzyme and pathway databases

ReactomeiR-HSA-6798695 Neutrophil degranulation
R-HSA-8951664 Neddylation
R-HSA-917937 Iron uptake and transport

Miscellaneous databases

ChiTaRSiCAND1 human
EvolutionaryTraceiQ86VP6
GeneWikiiCAND1
GenomeRNAii55832
PROiPR:Q86VP6
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111530 Expressed in 231 organ(s), highest expression level in kidney
ExpressionAtlasiQ86VP6 baseline and differential
GenevisibleiQ86VP6 HS

Family and domain databases

Gene3Di1.25.10.10, 2 hits
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR013932 TATA-bd_TIP120
PfamiView protein in Pfam
PF08623 TIP120, 1 hit
SUPFAMiSSF48371 SSF48371, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCAND1_HUMAN
AccessioniPrimary (citable) accession number: Q86VP6
Secondary accession number(s): B2RAU3
, O94918, Q6PIY4, Q8NDJ4, Q96JZ9, Q96T19, Q9BTC4, Q9H0G2, Q9P0H7, Q9UF85
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 7, 2005
Last sequence update: June 7, 2005
Last modified: September 12, 2018
This is version 158 of the entry and version 2 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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