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Protein

Nuclear-interacting partner of ALK

Gene

ZC3HC1

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

Functioni

Essential component of a SCF-type E3 ligase complex, SCF(NIPA), a complex that controls mitotic entry by mediating ubiquitination and subsequent degradation of cyclin B1 (CCNB1). Its cell-cycle-dependent phosphorylation regulates the assembly of the SCF(NIPA) complex, restricting CCNB1 ubiquitination activity to interphase. Its inactivation results in nuclear accumulation of CCNB1 in interphase and premature mitotic entry. May have an antiapoptotic role in NPM-ALK-mediated signaling events.1 Publication

Caution

Reported to contain a F-box domain (PubMed:16009132). Such domain is however not predicted by any detection method.1 Publication

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri102 – 156C3HC-typeAdd BLAST55

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Biological processCell cycle, Cell division, Mitosis, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

SIGNORiQ86WB0
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear-interacting partner of ALK
Alternative name(s):
Nuclear-interacting partner of anaplastic lymphoma kinase
Short name:
hNIPA
Zinc finger C3HC-type protein 1
Gene namesi
Name:ZC3HC1
Synonyms:NIPA
ORF Names:HSPC216
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000091732.15
HGNCiHGNC:29913 ZC3HC1
neXtProtiNX_Q86WB0

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

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi105Y → F: Does not strongly affect phosphorylation status; when associated with F-137. 1 Publication1
Mutagenesisi137Y → F: Does not strongly affect phosphorylation status; when associated with F-105. 1 Publication1
Mutagenesisi170 – 171LP → FM: Abolishes interaction with SKP1. 1 Publication2
Mutagenesisi354S → A: Strongly reduces phosphorylation and induces the formation of a constitutive SCF(NIPA) E3 complex that degrades CCNB1 at G2/M phase and delays mitotic entry. 2 Publications1
Mutagenesisi398 – 401RKAK → AAAA: Induces a complete cytoplasmic redistribution. 1 Publication4
Mutagenesisi399K → P: Induces a partial cytoplasmic redistribution. 1 Publication1

Organism-specific databases

DisGeNETi51530
OpenTargetsiENSG00000091732
PharmGKBiPA134931869

Polymorphism and mutation databases

BioMutaiZC3HC1
DMDMi73921220

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000968492 – 502Nuclear-interacting partner of ALKAdd BLAST501

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei24PhosphoserineCombined sources1
Modified residuei28PhosphothreonineCombined sources1
Modified residuei58PhosphoserineCombined sources1
Modified residuei62PhosphoserineCombined sources1
Modified residuei84PhosphothreonineCombined sources1
Modified residuei321PhosphoserineCombined sources1
Modified residuei329PhosphoserineCombined sources1
Modified residuei333PhosphothreonineCombined sources1
Modified residuei335PhosphoserineCombined sources1
Modified residuei338PhosphoserineCombined sources1
Modified residuei344PhosphoserineCombined sources1
Modified residuei354PhosphoserineCombined sources1 Publication1
Modified residuei359PhosphoserineCombined sources1
Modified residuei370PhosphoserineCombined sources1
Modified residuei381PhosphoserineCombined sources1
Modified residuei384PhosphothreonineCombined sources1
Modified residuei387PhosphothreonineCombined sources1
Modified residuei395PhosphoserineCombined sources1
Modified residuei407PhosphoserineCombined sources1
Modified residuei483PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated. Phosphorylated on Ser residues at G2/M phase, but not during S and G0 phases. May also be weakly phosphorylated on Tyr residues. Ser-354 phosphorylation, a major site during the course of cell-cycle-dedendent phosphorylation, results in its dissociation from the SCF(NIPA) complex, thereby preventing CCNB1 degradation leading to mitotic entry.2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ86WB0
MaxQBiQ86WB0
PaxDbiQ86WB0
PeptideAtlasiQ86WB0
PRIDEiQ86WB0
ProteomicsDBi70140
70141 [Q86WB0-2]
70142 [Q86WB0-3]

PTM databases

iPTMnetiQ86WB0
PhosphoSitePlusiQ86WB0
SwissPalmiQ86WB0

Expressioni

Tissue specificityi

Widely expressed. Highly expressed in heart, skeletal muscle and testis. Expressed in brain, placenta, lung, kidney, liver, pancreas, spleen, thymus, prostate, ovary small intestine and colon. Weakly or not expressed in leukocytes.1 Publication

Developmental stagei

Weakly expressed in G0/G1 phases, abundant during S and G2/M phases, and strongly decreases thereafter.1 Publication

Gene expression databases

BgeeiENSG00000091732 Expressed in 188 organ(s), highest expression level in quadriceps femoris
CleanExiHS_ZC3HC1
ExpressionAtlasiQ86WB0 baseline and differential
GenevisibleiQ86WB0 HS

Organism-specific databases

HPAiHPA019089
HPA024023

Interactioni

Subunit structurei

Interacts with the NPM-ALK fusion protein in a tyrosine phosphorylation-dependent manner. Interacts with SKP1. Component of a SCF(NIPA) E3 complex with SKP1, RBX1 and CUL1 when not phosphorylated on Ser-354. Interacts with CCNB1.2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi119592, 37 interactors
CORUMiQ86WB0
IntActiQ86WB0, 4 interactors
MINTiQ86WB0
STRINGi9606.ENSP00000351052

Structurei

3D structure databases

ProteinModelPortaliQ86WB0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni170 – 210F-box-likeAdd BLAST41

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi396 – 402Nuclear localization signal1 Publication7

Domaini

The F-box-like region is required for the interaction with SKP1.1 Publication

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri102 – 156C3HC-typeAdd BLAST55

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4765 Eukaryota
ENOG410ZQX4 LUCA
GeneTreeiENSGT00390000006086
HOVERGENiHBG082030
InParanoidiQ86WB0
OMAiAQHRDWC
OrthoDBiEOG091G0HKR
PhylomeDBiQ86WB0
TreeFamiTF314674

Family and domain databases

InterProiView protein in InterPro
IPR013909 NIPA/Rsm1
IPR012935 Znf_C3HC-like
PfamiView protein in Pfam
PF08600 Rsm1, 1 hit
PF07967 zf-C3HC, 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 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q86WB0-1) [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
MAAPCEGQAF AVGVEKNWGA VVRSPEGTPQ KIRQLIDEGI APEEGGVDAK
60 70 80 90 100
DTSATSQSVN GSPQAEQPSL ESTSKEAFFS RVETFSSLKW AGKPFELSPL
110 120 130 140 150
VCAKYGWVTV ECDMLKCSSC QAFLCASLQP AFDFDRYKQR CAELKKALCT
160 170 180 190 200
AHEKFCFWPD SPSPDRFGML PLDEPAILVS EFLDRFQSLC HLDLQLPSLR
210 220 230 240 250
PEDLKTMCLT EDKISLLLHL LEDELDHRTD ERKTTIKLGS DIQVHVTACI
260 270 280 290 300
LSVCGWACSS SLESMQLSLI TCSQCMRKVG LWGFQQIESS MTDLDASFGL
310 320 330 340 350
TSSPIPGLEG RPERLPLVPE SPRRMMTRSQ DATFSPGSEQ AEKSPGPIVS
360 370 380 390 400
RTRSWDSSSP VDRPEPEAAS PTTRTRPVTR SMGTGDTPGL EVPSSPLRKA
410 420 430 440 450
KRARLCSSSS SDTSSRSFFD PTSQHRDWCP WVNITLGKES RENGGTEPDA
460 470 480 490 500
SAPAEPGWKA VLTILLAHKQ SSQPAETDSM SLSEKSRKVF RIFRQWESLC

SC
Length:502
Mass (Da):55,262
Last modified:June 1, 2003 - v1
Checksum:iD5DEDF9E30070586
GO
Isoform 2 (identifier: Q86WB0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: MAAPCEGQAF...IAPEEGGVDA → MRGLPRKREAWTQPHPLEALYESLRVLE

Note: No experimental confirmation available.
Show »
Length:481
Mass (Da):53,559
Checksum:iB0EF4F07386A8554
GO
Isoform 3 (identifier: Q86WB0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     341-411: Missing.

Note: No experimental confirmation available.
Show »
Length:431
Mass (Da):47,771
Checksum:iEC1DCB8077C127C7
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J0I9C9J0I9_HUMAN
Nuclear-interacting partner of ALK
ZC3HC1
459Annotation score:
F8WDK5F8WDK5_HUMAN
Nuclear-interacting partner of ALK
ZC3HC1
50Annotation score:
F8WBD7F8WBD7_HUMAN
Nuclear-interacting partner of ALK
ZC3HC1
49Annotation score:
F8WF13F8WF13_HUMAN
Nuclear-interacting partner of ALK
ZC3HC1
53Annotation score:
F8WAU5F8WAU5_HUMAN
Nuclear-interacting partner of ALK
ZC3HC1
95Annotation score:

Sequence cautioni

The sequence AAF36136 differs from that shown. Reason: Frameshift at positions 93, 187 and 220.Curated
The sequence AAH28917 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAS07546 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence AAS07547 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti179V → I in BAB14024 (PubMed:14702039).Curated1
Sequence conflicti278K → R in AAF36136 (PubMed:11042152).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023312271T → A1 PublicationCorresponds to variant dbSNP:rs1464890Ensembl.1
Natural variantiVAR_023313363R → H1 PublicationCorresponds to variant dbSNP:rs11556924Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0152171 – 49MAAPC…GGVDA → MRGLPRKREAWTQPHPLEAL YESLRVLE in isoform 2. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_015218341 – 411Missing in isoform 3. 1 PublicationAdd BLAST71

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ537494 mRNA Translation: CAD61161.1
AF151050 mRNA Translation: AAF36136.1 Frameshift.
AK001317 mRNA Translation: BAA91619.1
AK022373 mRNA Translation: BAB14024.1
AC073320 Genomic DNA Translation: AAS07546.1 Sequence problems.
AC073320 Genomic DNA Translation: AAS07547.1 Sequence problems.
AC087071 Genomic DNA No translation available.
BC011551 mRNA Translation: AAH11551.1
BC028917 mRNA Translation: AAH28917.1 Different initiation.
CCDSiCCDS34753.1 [Q86WB0-1]
CCDS64767.1 [Q86WB0-2]
CCDS75659.1 [Q86WB0-3]
RefSeqiNP_001269119.1, NM_001282190.1 [Q86WB0-2]
NP_001269120.1, NM_001282191.1 [Q86WB0-3]
NP_057562.3, NM_016478.4 [Q86WB0-1]
UniGeneiHs.194157

Genome annotation databases

EnsembliENST00000311873; ENSP00000309301; ENSG00000091732 [Q86WB0-2]
ENST00000358303; ENSP00000351052; ENSG00000091732 [Q86WB0-1]
ENST00000360708; ENSP00000353933; ENSG00000091732 [Q86WB0-3]
GeneIDi51530
KEGGihsa:51530
UCSCiuc003vpi.4 human [Q86WB0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ537494 mRNA Translation: CAD61161.1
AF151050 mRNA Translation: AAF36136.1 Frameshift.
AK001317 mRNA Translation: BAA91619.1
AK022373 mRNA Translation: BAB14024.1
AC073320 Genomic DNA Translation: AAS07546.1 Sequence problems.
AC073320 Genomic DNA Translation: AAS07547.1 Sequence problems.
AC087071 Genomic DNA No translation available.
BC011551 mRNA Translation: AAH11551.1
BC028917 mRNA Translation: AAH28917.1 Different initiation.
CCDSiCCDS34753.1 [Q86WB0-1]
CCDS64767.1 [Q86WB0-2]
CCDS75659.1 [Q86WB0-3]
RefSeqiNP_001269119.1, NM_001282190.1 [Q86WB0-2]
NP_001269120.1, NM_001282191.1 [Q86WB0-3]
NP_057562.3, NM_016478.4 [Q86WB0-1]
UniGeneiHs.194157

3D structure databases

ProteinModelPortaliQ86WB0
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119592, 37 interactors
CORUMiQ86WB0
IntActiQ86WB0, 4 interactors
MINTiQ86WB0
STRINGi9606.ENSP00000351052

PTM databases

iPTMnetiQ86WB0
PhosphoSitePlusiQ86WB0
SwissPalmiQ86WB0

Polymorphism and mutation databases

BioMutaiZC3HC1
DMDMi73921220

Proteomic databases

EPDiQ86WB0
MaxQBiQ86WB0
PaxDbiQ86WB0
PeptideAtlasiQ86WB0
PRIDEiQ86WB0
ProteomicsDBi70140
70141 [Q86WB0-2]
70142 [Q86WB0-3]

Protocols and materials databases

DNASUi51530
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000311873; ENSP00000309301; ENSG00000091732 [Q86WB0-2]
ENST00000358303; ENSP00000351052; ENSG00000091732 [Q86WB0-1]
ENST00000360708; ENSP00000353933; ENSG00000091732 [Q86WB0-3]
GeneIDi51530
KEGGihsa:51530
UCSCiuc003vpi.4 human [Q86WB0-1]

Organism-specific databases

CTDi51530
DisGeNETi51530
EuPathDBiHostDB:ENSG00000091732.15
GeneCardsiZC3HC1
H-InvDBiHIX0007070
HGNCiHGNC:29913 ZC3HC1
HPAiHPA019089
HPA024023
neXtProtiNX_Q86WB0
OpenTargetsiENSG00000091732
PharmGKBiPA134931869
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4765 Eukaryota
ENOG410ZQX4 LUCA
GeneTreeiENSGT00390000006086
HOVERGENiHBG082030
InParanoidiQ86WB0
OMAiAQHRDWC
OrthoDBiEOG091G0HKR
PhylomeDBiQ86WB0
TreeFamiTF314674

Enzyme and pathway databases

UniPathwayi
UPA00143

SIGNORiQ86WB0

Miscellaneous databases

ChiTaRSiZC3HC1 human
GeneWikiiZC3HC1
GenomeRNAii51530
PROiPR:Q86WB0

Gene expression databases

BgeeiENSG00000091732 Expressed in 188 organ(s), highest expression level in quadriceps femoris
CleanExiHS_ZC3HC1
ExpressionAtlasiQ86WB0 baseline and differential
GenevisibleiQ86WB0 HS

Family and domain databases

InterProiView protein in InterPro
IPR013909 NIPA/Rsm1
IPR012935 Znf_C3HC-like
PfamiView protein in Pfam
PF08600 Rsm1, 1 hit
PF07967 zf-C3HC, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNIPA_HUMAN
AccessioniPrimary (citable) accession number: Q86WB0
Secondary accession number(s): A6NH66
, Q75MF3, Q75MF4, Q8N330, Q96F75, Q9HA34, Q9NVX4, Q9P0R0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: June 1, 2003
Last modified: November 7, 2018
This is version 138 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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