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

PAX-interacting protein 1

Gene

PAXIP1

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

Functioni

Involved in DNA damage response and in transcriptional regulation through histone methyltransferase (HMT) complexes. Plays a role in early development. In DNA damage response is required for cell survival after ionizing radiation. In vitro shown to be involved in the homologous recombination mechanism for the repair of double-strand breaks (DSBs). Its localization to DNA damage foci requires RNF8 and UBE2N. Recruits TP53BP1 to DNA damage foci and, at least in particular repair processes, effective DNA damage response appears to require the association with TP53BP1 phosphorylated by ATM at 'Ser-25'. Together with TP53BP1 regulates ATM association. Proposed to recruit PAGR1 to sites of DNA damage and the PAGR1:PAXIP1 complex is required for cell survival in response to DNA damage; the function is probably independent of MLL-containing histone methyltransferase (HMT) complexes. However, this function has been questioned (By similarity). Promotes ubiquitination of PCNA following UV irradiation and may regulate recruitment of polymerase eta and RAD51 to chromatin after DNA damage. Proposed to be involved in transcriptional regulation by linking MLL-containing histone methyltransferase (HMT) complexes to gene promoters by interacting with promoter-bound transcription factors such as PAX2. Associates with gene promoters that are known to be regulated by KMT2D/MLL2. During immunoglobulin class switching in activated B-cells is involved in trimethylation of histone H3 at 'Lys-4' and in transcription initiation of downstream switch regions at the immunoglobulin heavy-chain (Igh) locus; this function appears to involve the recruitment of MLL-containing HMT complexes. Conflictingly, its function in transcriptional regulation during immunoglobulin class switching is reported to be independent of the MLL2/MLL3 complex (By similarity).By similarity7 Publications

Caution

The terminology of MLL proteins in mammalia is not consistent also concerning the terminology of MLL protein-containing complexes. The decribed MLL2/MLL3 complex is commonly described as MLL3/MLL4 complex in literature.Curated

GO - Biological processi

Keywordsi

Biological processDNA damage, DNA recombination, DNA repair, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
SignaLinkiQ6ZW49
SIGNORiQ6ZW49

Names & Taxonomyi

Protein namesi
Recommended name:
PAX-interacting protein 1
Alternative name(s):
PAX transactivation activation domain-interacting protein
Gene namesi
Name:PAXIP1
Synonyms:PAXIP1L, PTIP
ORF Names:CAGF28
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000157212.18
HGNCiHGNC:8624 PAXIP1
MIMi608254 gene
neXtProtiNX_Q6ZW49

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

Chromosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi676W → A: Abolishes interaction with TP53BP1; prevents recruitment to DNA damage foci. 1 Publication1
Mutagenesisi910R → Q: Abolishes interaction with TP53BP1; impairs intact cellular response to DNA damage. 1 Publication1
Mutagenesisi929W → A: Abolishes interaction with TP53BP1; prevents recruitment to DNA damage foci. 1 Publication1

Organism-specific databases

DisGeNETi22976
MalaCardsiPAXIP1
OpenTargetsiENSG00000157212
PharmGKBiPA32964

Polymorphism and mutation databases

BioMutaiPAXIP1
DMDMi317373316

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002962621 – 1069PAX-interacting protein 1Add BLAST1069

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei227PhosphoserineBy similarity1
Modified residuei235PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6ZW49
MaxQBiQ6ZW49
PaxDbiQ6ZW49
PeptideAtlasiQ6ZW49
PRIDEiQ6ZW49
ProteomicsDBi68459
68460 [Q6ZW49-1]
68461 [Q6ZW49-2]

PTM databases

iPTMnetiQ6ZW49
PhosphoSitePlusiQ6ZW49

Expressioni

Gene expression databases

BgeeiENSG00000157212 Expressed in 207 organ(s), highest expression level in secondary oocyte
CleanExiHS_PAXIP1
ExpressionAtlasiQ6ZW49 baseline and differential
GenevisibleiQ6ZW49 HS

Organism-specific databases

HPAiHPA006694
HPA016950

Interactioni

Subunit structurei

Interacts with the C-terminal transactivation domain of PAX2 (By similarity). Forms a constitutive complex with PAGR1 independently of the MLL2/MLL3 complex (By similarity). Interacts with TP53BP1 (when phosphorylated at the N-terminus by ATM) (PubMed:15456759, PubMed:17690115, PubMed:23727112). Interacts with HLTF (PubMed:19723507). Component of the KMT2 family MLL2/MLL3 complex (also named ASCOM complex), at least composed of the HMTs KMT2D and/or KMT2C, the common subunits ASH2L, RBBP5, WDR5 and DPY30, and the complex type-specific subunits PAXIP1/PTIP, PAGR1, NCOA6 and KDM6A; required for the association of PAGR1 with the MLL2/MLL3 complex (PubMed:17178841, PubMed:17500065, PubMed:17761849, PubMed:17925232).By similarity8 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi116625, 264 interactors
CORUMiQ6ZW49
DIPiDIP-41786N
IntActiQ6ZW49, 32 interactors
MINTiQ6ZW49
STRINGi9606.ENSP00000384048

Structurei

Secondary structure

11069
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ6ZW49
SMRiQ6ZW49
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini8 – 93BRCT 1PROSITE-ProRule annotationAdd BLAST86
Domaini94 – 183BRCT 2PROSITE-ProRule annotationAdd BLAST90
Domaini601 – 694BRCT 3PROSITE-ProRule annotationAdd BLAST94
Domaini703 – 779BRCT 4PROSITE-ProRule annotationAdd BLAST77
Domaini866 – 947BRCT 5PROSITE-ProRule annotationAdd BLAST82
Domaini970 – 1059BRCT 6PROSITE-ProRule annotationAdd BLAST90

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni94 – 183Interaction with PAGR1By similarityAdd BLAST90
Regioni590 – 1069Interaction with TP53BP1Add BLAST480

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi702 – 719Nuclear localization signalSequence analysisAdd BLAST18

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi223 – 250Glu-richAdd BLAST28
Compositional biasi406 – 624Gln-richAdd BLAST219

Domaini

The BRCT 1 and 2 domains mediate the interaction with PAGR1A.By similarity
The BRCT 5 and 6 domains mediate the association with the MLL2/MLL3 complex (By similarity). The BRCT 5 and 6 domains function as a single module and are necessary and sufficient for in vitro phospho-specific binding (substrates phosphorylated by the kinases ataxia telangiectasia-mutated (ATM), ataxia telangiectasia and RAD3-related (ATR) in response to gamma irradiation). In contrast, in vivo two pairs of BRCT domains (3-6) bind to phosphorylated TP53BP1 much more efficiently.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG2043 Eukaryota
ENOG410XSGS LUCA
GeneTreeiENSGT00600000084454
HOVERGENiHBG061191
InParanoidiQ6ZW49
KOiK14972
OMAiFKCQKFV
OrthoDBiEOG091G0YK0
PhylomeDBiQ6ZW49
TreeFamiTF329580

Family and domain databases

CDDicd00027 BRCT, 4 hits
Gene3Di3.40.50.10190, 5 hits
InterProiView protein in InterPro
IPR001357 BRCT_dom
IPR036420 BRCT_dom_sf
PfamiView protein in Pfam
PF00533 BRCT, 1 hit
PF12738 PTCB-BRCT, 2 hits
PF16770 RTT107_BRCT_5, 1 hit
SMARTiView protein in SMART
SM00292 BRCT, 5 hits
SUPFAMiSSF52113 SSF52113, 5 hits
PROSITEiView protein in PROSITE
PS50172 BRCT, 5 hits

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q6ZW49-6) [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
MSDQAPKVPE EMFREVKYYA VGDIDPQVIQ LLKAGKAKEV SYNALASHII
60 70 80 90 100
SEDGDNPEVG EAREVFDLPV VKPSWVILSV QCGTLLPVNG FSPESCQIFF
110 120 130 140 150
GITACLSQVS SEDRSALWAL VTFYGGDCQL TLNKKCTHLI VPEPKGEKYE
160 170 180 190 200
CALKRASIKI VTPDWVLDCV SEKTKKDEAF YHPRLIIYEE EEEEEEEEEE
210 220 230 240 250
VENEEQDSQN EGSTDEKSSP ASSQEGSPSG DQQFSPKSNT EKSKGELMFD
260 270 280 290 300
DSSDSSPEKQ ERNLNWTPAE VPQLAAAKRR LPQGKEPGLI NLCANVPPVP
310 320 330 340 350
GNILPPEVRG NLMAAGQNLQ SSERSEMIAT WSPAVRTLRN ITNNADIQQM
360 370 380 390 400
NRPSNVAHIL QTLSAPTKNL EQQVNHSQQG HTNANAVLFS QVKVTPETHM
410 420 430 440 450
LQQQQQAQQQ QQQHPVLHLQ PQQIMQLQQQ QQQQISQQPY PQQPPHPFSQ
460 470 480 490 500
QQQQQQQAHP HQFSQQQLQF PQQQLHPPQQ LHRPQQQLQP FQQQHALQQQ
510 520 530 540 550
FHQLQQHQLQ QQQLAQLQQQ HSLLQQQQQQ QIQQQQLQRM HQQQQQQQMQ
560 570 580 590 600
SQTAPHLSQT SQALQHQVPP QQPPQQQQQQ QPPPSPQQHQ LFGHDPAVEI
610 620 630 640 650
PEEGFLLGCV FAIADYPEQM SDKQLLATWK RIIQAHGGTV DPTFTSRCTH
660 670 680 690 700
LLCESQVSSA YAQAIRERKR CVTAHWLNTV LKKKKMVPPH RALHFPVAFP
710 720 730 740 750
PGGKPCSQHI ISVTGFVDSD RDDLKLMAYL AGAKYTGYLC RSNTVLICKE
760 770 780 790 800
PTGLKYEKAK EWRIPCVNAQ WLGDILLGNF EALRQIQYSR YTAFSLQDPF
810 820 830 840 850
APTQHLVLNL LDAWRVPLKV SAELLMSIRL PPKLKQNEVA NVQPSSKRAR
860 870 880 890 900
IEDVPPPTKK LTPELTPFVL FTGFEPVQVQ QYIKKLYILG GEVAESAQKC
910 920 930 940 950
THLIASKVTR TVKFLTAISV VKHIVTPEWL EECFRCQKFI DEQNYILRDA
960 970 980 990 1000
EAEVLFSFSL EESLKRAHVS PLFKAKYFYI TPGICPSLST MKAIVECAGG
1010 1020 1030 1040 1050
KVLSKQPSFR KLMEHKQNSS LSEIILISCE NDLHLCREYF ARGIDVHNAE
1060
FVLTGVLTQT LDYESYKFN
Length:1,069
Mass (Da):121,341
Last modified:January 11, 2011 - v2
Checksum:i78CD535A150E1FC1
GO
Isoform 2 (identifier: Q6ZW49-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-108: MSDQAPKVPE...FFGITACLSQ → MVFLQNHVRF...QAEASVVMCW

Show »
Length:1,035
Mass (Da):117,690
Checksum:i3AB758354881AF7D
GO
Isoform 3 (identifier: Q6ZW49-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-247: Missing.

Note: No experimental confirmation available.
Show »
Length:822
Mass (Da):93,882
Checksum:i06D81BB07A314ED0
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7BZI8H7BZI8_HUMAN
PAX-interacting protein 1
PAXIP1
173Annotation score:
F8WC23F8WC23_HUMAN
PAX-interacting protein 1
PAXIP1
147Annotation score:

Sequence cautioni

The sequence AAB91434 differs from that shown. Reason: Frameshift at positions 643 and 662.Curated
The sequence AAH33781 differs from that shown. Contaminating sequence.Curated
The sequence AAH33781 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAP21865 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence BAC85523 differs from that shown. Intron retention.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti121V → D in AK307417 (PubMed:14702039).Curated1
Sequence conflicti154K → R in CAE45762 (PubMed:17974005).Curated1
Sequence conflicti260Q → H in CAE45762 (PubMed:17974005).Curated1
Sequence conflicti406Missing in AK307417 (PubMed:14702039).Curated1
Sequence conflicti458 – 581Missing in AAB91434 (PubMed:9225980).CuratedAdd BLAST124
Sequence conflicti847K → Q in AAB91434 (PubMed:9225980).Curated1
Sequence conflicti912V → L in AAB91434 (PubMed:9225980).Curated1
Sequence conflicti916T → A in AAB91434 (PubMed:9225980).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0346271013M → V1 PublicationCorresponds to variant dbSNP:rs3501Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0403031 – 247Missing in isoform 3. 1 PublicationAdd BLAST247
Alternative sequenceiVSP_0403001 – 108MSDQA…ACLSQ → MVFLQNHVRFFLESLPAFLR VLIQAGALCWSLPELSQGEV GKGACPAEVGKHRDHLPSSD PVLMQAEASVVMCW in isoform 2. 1 PublicationAdd BLAST108

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK123044 mRNA Translation: BAC85523.1 Sequence problems.
AK123600 mRNA Translation: BAC85657.1
AK307417 mRNA No translation available.
BX538201 mRNA Translation: CAD98066.1
BX640616 mRNA Translation: CAE45762.1
AC093726 Genomic DNA Translation: AAP21865.1 Sequence problems.
U80735 mRNA Translation: AAB91434.1 Frameshift.
BC008328 mRNA Translation: AAH08328.1
BC033781 mRNA Translation: AAH33781.1 Sequence problems.
CCDSiCCDS47753.1 [Q6ZW49-6]
RefSeqiNP_031375.3, NM_007349.3 [Q6ZW49-6]
XP_005249596.1, XM_005249539.1 [Q6ZW49-1]
XP_016867370.1, XM_017011881.1 [Q6ZW49-1]
UniGeneiHs.443881

Genome annotation databases

EnsembliENST00000397192; ENSP00000380376; ENSG00000157212 [Q6ZW49-6]
ENST00000404141; ENSP00000384048; ENSG00000157212 [Q6ZW49-6]
GeneIDi22976
KEGGihsa:22976
UCSCiuc033aqm.2 human [Q6ZW49-6]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK123044 mRNA Translation: BAC85523.1 Sequence problems.
AK123600 mRNA Translation: BAC85657.1
AK307417 mRNA No translation available.
BX538201 mRNA Translation: CAD98066.1
BX640616 mRNA Translation: CAE45762.1
AC093726 Genomic DNA Translation: AAP21865.1 Sequence problems.
U80735 mRNA Translation: AAB91434.1 Frameshift.
BC008328 mRNA Translation: AAH08328.1
BC033781 mRNA Translation: AAH33781.1 Sequence problems.
CCDSiCCDS47753.1 [Q6ZW49-6]
RefSeqiNP_031375.3, NM_007349.3 [Q6ZW49-6]
XP_005249596.1, XM_005249539.1 [Q6ZW49-1]
XP_016867370.1, XM_017011881.1 [Q6ZW49-1]
UniGeneiHs.443881

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3SQDX-ray2.15A/B860-1069[»]
ProteinModelPortaliQ6ZW49
SMRiQ6ZW49
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116625, 264 interactors
CORUMiQ6ZW49
DIPiDIP-41786N
IntActiQ6ZW49, 32 interactors
MINTiQ6ZW49
STRINGi9606.ENSP00000384048

PTM databases

iPTMnetiQ6ZW49
PhosphoSitePlusiQ6ZW49

Polymorphism and mutation databases

BioMutaiPAXIP1
DMDMi317373316

Proteomic databases

EPDiQ6ZW49
MaxQBiQ6ZW49
PaxDbiQ6ZW49
PeptideAtlasiQ6ZW49
PRIDEiQ6ZW49
ProteomicsDBi68459
68460 [Q6ZW49-1]
68461 [Q6ZW49-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000397192; ENSP00000380376; ENSG00000157212 [Q6ZW49-6]
ENST00000404141; ENSP00000384048; ENSG00000157212 [Q6ZW49-6]
GeneIDi22976
KEGGihsa:22976
UCSCiuc033aqm.2 human [Q6ZW49-6]

Organism-specific databases

CTDi22976
DisGeNETi22976
EuPathDBiHostDB:ENSG00000157212.18
GeneCardsiPAXIP1
H-InvDBiHIX0007243
HGNCiHGNC:8624 PAXIP1
HPAiHPA006694
HPA016950
MalaCardsiPAXIP1
MIMi608254 gene
neXtProtiNX_Q6ZW49
OpenTargetsiENSG00000157212
PharmGKBiPA32964
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2043 Eukaryota
ENOG410XSGS LUCA
GeneTreeiENSGT00600000084454
HOVERGENiHBG061191
InParanoidiQ6ZW49
KOiK14972
OMAiFKCQKFV
OrthoDBiEOG091G0YK0
PhylomeDBiQ6ZW49
TreeFamiTF329580

Enzyme and pathway databases

ReactomeiR-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-5693571 Nonhomologous End-Joining (NHEJ)
SignaLinkiQ6ZW49
SIGNORiQ6ZW49

Miscellaneous databases

ChiTaRSiPAXIP1 human
GeneWikiiPAXIP1
GenomeRNAii22976
PROiPR:Q6ZW49
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000157212 Expressed in 207 organ(s), highest expression level in secondary oocyte
CleanExiHS_PAXIP1
ExpressionAtlasiQ6ZW49 baseline and differential
GenevisibleiQ6ZW49 HS

Family and domain databases

CDDicd00027 BRCT, 4 hits
Gene3Di3.40.50.10190, 5 hits
InterProiView protein in InterPro
IPR001357 BRCT_dom
IPR036420 BRCT_dom_sf
PfamiView protein in Pfam
PF00533 BRCT, 1 hit
PF12738 PTCB-BRCT, 2 hits
PF16770 RTT107_BRCT_5, 1 hit
SMARTiView protein in SMART
SM00292 BRCT, 5 hits
SUPFAMiSSF52113 SSF52113, 5 hits
PROSITEiView protein in PROSITE
PS50172 BRCT, 5 hits
ProtoNetiSearch...

Entry informationi

Entry nameiPAXI1_HUMAN
AccessioniPrimary (citable) accession number: Q6ZW49
Secondary accession number(s): O15404
, Q6N099, Q6ZWH9, Q7Z315, Q86UN0, Q8N4P9, Q96HP2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 24, 2007
Last sequence update: January 11, 2011
Last modified: November 7, 2018
This is version 126 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, 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again