Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Nuclear-interacting partner of ALK

Gene

ZC3HC1

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

Functioni

Essential component of an 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

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

Complete GO annotation...

Keywords - Biological processi

Cell cycle, Cell division, Mitosis, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

SIGNORiQ86WB0.
UniPathwayiUPA00143.

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

HGNCiHGNC:29913. ZC3HC1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.

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.
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 kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi119592. 34 interactors.
IntActiQ86WB0. 4 interactors.
MINTiMINT-4539594.
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

Sequence similaritiesi

Contains 1 C3HC-type zinc finger.Curated

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.
OMAiYSLKWAG.
OrthoDBiEOG091G0HKR.
PhylomeDBiQ86WB0.
TreeFamiTF314674.

Family and domain databases

InterProiIPR013909. NIPA/Rsm1.
IPR012935. Znf_C3HC-like.
[Graphical view]
PfamiPF08600. Rsm1. 1 hit.
PF07967. zf-C3HC. 1 hit.
[Graphical view]

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

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

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 → A.1 PublicationCorresponds to variant rs1464890dbSNPEnsembl.1
Natural variantiVAR_023313363R → H.1 PublicationCorresponds to variant rs11556924dbSNPEnsembl.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

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. 34 interactors.
IntActiQ86WB0. 4 interactors.
MINTiMINT-4539594.
STRINGi9606.ENSP00000351052.

PTM databases

iPTMnetiQ86WB0.
PhosphoSitePlusiQ86WB0.
SwissPalmiQ86WB0.

Polymorphism and mutation databases

BioMutaiZC3HC1.
DMDMi73921220.

Proteomic databases

EPDiQ86WB0.
MaxQBiQ86WB0.
PaxDbiQ86WB0.
PeptideAtlasiQ86WB0.
PRIDEiQ86WB0.

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.
GeneCardsiZC3HC1.
H-InvDBHIX0007070.
HGNCiHGNC:29913. ZC3HC1.
HPAiHPA019089.
HPA024023.
neXtProtiNX_Q86WB0.
OpenTargetsiENSG00000091732.
PharmGKBiPA134931869.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4765. Eukaryota.
ENOG410ZQX4. LUCA.
GeneTreeiENSGT00390000006086.
HOVERGENiHBG082030.
InParanoidiQ86WB0.
OMAiYSLKWAG.
OrthoDBiEOG091G0HKR.
PhylomeDBiQ86WB0.
TreeFamiTF314674.

Enzyme and pathway databases

UniPathwayiUPA00143.
SIGNORiQ86WB0.

Miscellaneous databases

ChiTaRSiZC3HC1. human.
GeneWikiiZC3HC1.
GenomeRNAii51530.
PROiQ86WB0.

Gene expression databases

BgeeiENSG00000091732.
CleanExiHS_ZC3HC1.
ExpressionAtlasiQ86WB0. baseline and differential.
GenevisibleiQ86WB0. HS.

Family and domain databases

InterProiIPR013909. NIPA/Rsm1.
IPR012935. Znf_C3HC-like.
[Graphical view]
PfamiPF08600. Rsm1. 1 hit.
PF07967. zf-C3HC. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNIPA_HUMAN
AccessioniPrimary (citable) accession number: Q86WB0
Secondary accession number(s): A6NH66
, Q75MF3, Q75MF4, Q8N330, Q96F75, Q9HA34, Q9NVX4, Q9P0R0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: June 1, 2003
Last modified: November 2, 2016
This is version 124 of the entry and version 1 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

Caution

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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  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.