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Protein

Protein HIRA

Gene

HIRA

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

Functioni

Cooperates with ASF1A to promote replication-independent chromatin assembly. Required for the periodic repression of histone gene transcription during the cell cycle. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit.3 Publications

GO - Molecular functioni

  • DNA-binding transcription factor activity Source: ProtInc
  • nucleosome binding Source: GO_Central
  • transcription corepressor activity Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Repressor
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-2559584 Formation of Senescence-Associated Heterochromatin Foci (SAHF)
SignaLinkiP54198
SIGNORiP54198

Names & Taxonomyi

Protein namesi
Recommended name:
Protein HIRA
Alternative name(s):
TUP1-like enhancer of split protein 1
Gene namesi
Name:HIRA
Synonyms:DGCR1, HIR, TUPLE1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100084.14
HGNCiHGNC:4916 HIRA
MIMi600237 gene
neXtProtiNX_P54198

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
Mutagenesisi449 – 458Missing : Impairs binding to ASF1A. 1 Publication10
Mutagenesisi458 – 460RRR → AKK: Abrogates binding to ASF1A. 3
Mutagenesisi458 – 460RRR → KKK: Impairs binding to ASF1A. 3
Mutagenesisi458 – 459RR → AK: Impairs binding to ASF1A. 2
Mutagenesisi458R → A: Impairs binding to ASF1A. 1
Mutagenesisi458R → K: Impairs binding to ASF1A; when associated with K-460. 1
Mutagenesisi459 – 468Missing : Abrogates binding to ASF1A. 1 Publication10
Mutagenesisi459R → A: Abrogates binding to ASF1A. 1 Publication1
Mutagenesisi460R → A: Abrogates binding to ASF1A. 1 Publication1
Mutagenesisi460R → K: Impairs binding to ASF1A; when associated with K-458. 1 Publication1
Mutagenesisi461I → D: Abrogates binding to ASF1A. 1 Publication1
Mutagenesisi464L → D: Impairs binding to ASF1A. 1 Publication1
Mutagenesisi466I → D: Impairs binding to ASF1A. 1 Publication1
Mutagenesisi555T → A: Impairs phosphorylation by CDK2. 1 Publication1
Mutagenesisi628 – 631KRKL → AAAA: Impairs binding to CCNA1 and phosphorylation by CDK2. 1 Publication4

Organism-specific databases

DisGeNETi7290
MalaCardsiHIRA
OpenTargetsiENSG00000100084
Orphaneti567 22q11.2 deletion syndrome
PharmGKBiPA29293

Polymorphism and mutation databases

BioMutaiHIRA
DMDMi88984228

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000510191 – 1017Protein HIRAAdd BLAST1017

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei111PhosphoserineCombined sources1
Modified residuei549PhosphoserineCombined sources1
Modified residuei555Phosphothreonine; by CDK21 Publication1
Modified residuei557PhosphoserineCombined sources1
Modified residuei576PhosphothreonineCombined sources1
Modified residuei584PhosphoserineCombined sources1
Modified residuei586PhosphothreonineCombined sources1
Modified residuei610PhosphoserineCombined sources1
Modified residuei611PhosphoserineCombined sources1
Modified residuei612PhosphoserineCombined sources1
Modified residuei614PhosphoserineCombined sources1
Modified residuei661PhosphoserineCombined sources1
Modified residuei675PhosphoserineCombined sources1
Modified residuei687Phosphoserine1 Publication1

Post-translational modificationi

Sumoylated.1 Publication
Phosphorylated by CDK2/CCNA1 and CDK2/CCNE1 on Thr-555 in vitro. Also phosphorylated on Thr-555 and Ser-687 in vivo.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP54198
MaxQBiP54198
PaxDbiP54198
PeptideAtlasiP54198
PRIDEiP54198
ProteomicsDBi56652
56653 [P54198-2]

PTM databases

iPTMnetiP54198
PhosphoSitePlusiP54198

Expressioni

Tissue specificityi

Expressed at high levels in kidney, pancreas and skeletal muscle and at lower levels in brain, heart, liver, lung, and placenta.1 Publication

Developmental stagei

Expressed during embryogenesis.

Gene expression databases

BgeeiENSG00000100084 Expressed in 205 organ(s), highest expression level in thyroid gland
CleanExiHS_HIRA
ExpressionAtlasiP54198 baseline and differential
GenevisibleiP54198 HS

Organism-specific databases

HPAiCAB039243
CAB039244
HPA050714
HPA052902

Interactioni

Subunit structurei

Interacts with histone H3F3B, PAX3 and PAX7 (By similarity). Interacts with histone H3.Y (PubMed:28334823). Interacts with CCNA1, HIRIP3, NFU1/HIRIP5 and histone H2B. Part of a complex which includes ASF1A, CABIN1, histone H3.3, histone H4 and UBN1 (PubMed:11238922, PubMed:14680630, PubMed:14718166, PubMed:15621527, PubMed:16980972, PubMed:19029251, PubMed:9710638).By similarity8 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi113141, 39 interactors
CORUMiP54198
DIPiDIP-29240N
ELMiP54198
IntActiP54198, 19 interactors
MINTiP54198
STRINGi9606.ENSP00000263208

Structurei

Secondary structure

11017
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP54198
SMRiP54198
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP54198

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati11 – 53WD 1Add BLAST43
Repeati68 – 107WD 2Add BLAST40
Repeati129 – 168WD 3Add BLAST40
Repeati172 – 211WD 4Add BLAST40
Repeati220 – 263WD 5Add BLAST44
Repeati266 – 322WD 6Add BLAST57
Repeati326 – 367WD 7Add BLAST42

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni421 – 729Interaction with CCNA11 PublicationAdd BLAST309
Regioni421 – 479Interaction with ASF1AAdd BLAST59
Regioni439 – 475Required for repression of histone gene transcriptionAdd BLAST37
Regioni593 – 826Interaction with histone H2BAdd BLAST234
Regioni594 – 739Interaction with PAX3By similarityAdd BLAST146
Regioni738 – 1017Interaction with histone H4Add BLAST280
Regioni740 – 828Interaction with PAX3By similarityAdd BLAST89

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi408 – 412Poly-Gln5
Compositional biasi640 – 643Poly-Lys4
Compositional biasi805 – 808Poly-Val4

Sequence similaritiesi

Belongs to the WD repeat HIR1 family.Curated

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0973 Eukaryota
ENOG410XP1H LUCA
GeneTreeiENSGT00550000074919
HOGENOMiHOG000007670
HOVERGENiHBG005969
InParanoidiP54198
KOiK11293
OMAiLLGPVHY
OrthoDBiEOG091G04F0
PhylomeDBiP54198
TreeFamiTF323161

Family and domain databases

Gene3Di2.130.10.10, 2 hits
InterProiView protein in InterPro
IPR031120 HIR1
IPR011494 Hira
IPR019015 HIRA_B_motif
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PANTHERiPTHR13831 PTHR13831, 1 hit
PfamiView protein in Pfam
PF07569 Hira, 1 hit
PF09453 HIRA_B, 1 hit
PF00400 WD40, 4 hits
SMARTiView protein in SMART
SM00320 WD40, 7 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS00678 WD_REPEATS_1, 1 hit
PS50082 WD_REPEATS_2, 3 hits
PS50294 WD_REPEATS_REGION, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform Long (identifier: P54198-1) [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
MKLLKPTWVN HNGKPIFSVD IHPDGTKFAT GGQGQDSGKV VIWNMSPVLQ
60 70 80 90 100
EDDEKDENIP KMLCQMDNHL ACVNCVRWSN SGMYLASGGD DKLIMVWKRA
110 120 130 140 150
TYIGPSTVFG SSGKLANVEQ WRCVSILRNH SGDVMDVAWS PHDAWLASCS
160 170 180 190 200
VDNTVVIWNA VKFPEILATL RGHSGLVKGL TWDPVGKYIA SQADDRSLKV
210 220 230 240 250
WRTLDWQLET SITKPFDECG GTTHVLRLSW SPDGHYLVSA HAMNNSGPTA
260 270 280 290 300
QIIEREGWKT NMDFVGHRKA VTVVKFNPKI FKKKQKNGSS AKPSCPYCCC
310 320 330 340 350
AVGSKDRSLS VWLTCLKRPL VVIHELFDKS IMDISWTLNG LGILVCSMDG
360 370 380 390 400
SVAFLDFSQD ELGDPLSEEE KSRIHQSTYG KSLAIMTEAQ LSTAVIENPE
410 420 430 440 450
MLKYQRRQQQ QQLDQKSAAT REMGSATSVA GVVNGESLED IRKNLLKKQV
460 470 480 490 500
ETRTADGRRR ITPLCIAQLD TGDFSTAFFN SIPLSGSLAG TMLSSHSSPQ
510 520 530 540 550
LLPLDSSTPN SFGASKPCTE PVVAASARPA GDSVNKDSMN ATSTPAALSP
560 570 580 590 600
SVLTTPSKIE PMKAFDSRFT ERSKATPGAP ALTSMTPTAV ERLKEQNLVK
610 620 630 640 650
ELRPRDLLES SSDSDEKVPL AKASSLSKRK LELEVETVEK KKKGRPRKDS
660 670 680 690 700
RLMPVSLSVQ SPAALTAEKE AMCLSAPALA LKLPIPSPQR AFTLQVSSDP
710 720 730 740 750
SMYIEVENEV TVVGGVKLSR LKCNREGKEW ETVLTSRILT AAGSCDVVCV
760 770 780 790 800
ACEKRMLSVF STCGRRLLSP ILLPSPISTL HCTGSYVMAL TAAATLSVWD
810 820 830 840 850
VHRQVVVVKE ESLHSILAGS DMTVSQILLT QHGIPVMNLS DGKAYCFNPS
860 870 880 890 900
LSTWNLVSDK QDSLAQCADF RSSLPSQDAM LCSGPLAIIQ GRTSNSGRQA
910 920 930 940 950
ARLFSVPHVV QQETTLAYLE NQVAAALTLQ SSHEYRHWLL VYARYLVNEG
960 970 980 990 1000
FEYRLREICK DLLGPVHYST GSQWESTVVG LRKRELLKEL LPVIGQNLRF
1010
QRLFTECQEQ LDILRDK
Length:1,017
Mass (Da):111,835
Last modified:February 21, 2006 - v2
Checksum:i475784B2FF9D16D6
GO
Isoform Short (identifier: P54198-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     593-799: Missing.

Show »
Length:810
Mass (Da):89,299
Checksum:iA169BFDCE4C8D4D7
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H7C2A7H7C2A7_HUMAN
Protein HIRA
HIRA
53Annotation score:

Sequence cautioni

The sequence CAA53044 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAA54721 differs from that shown. Reason: Erroneous initiation.Curated
The sequence CAA57436 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti9V → G in CAA54721 (PubMed:7633437).Curated1
Sequence conflicti889I → N in CAA54721 (PubMed:7633437).Curated1
Sequence conflicti889I → N in CAA57436 (PubMed:7633437).Curated1
Sequence conflicti889I → N in CAA61979 (PubMed:8681138).Curated1
Sequence conflicti990L → M in CAA53044 (PubMed:8111380).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006772593 – 799Missing in isoform Short. 1 PublicationAdd BLAST207

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81844 mRNA Translation: CAA57436.1 Different initiation.
X77633 mRNA Translation: CAA54721.1 Different initiation.
X89887 mRNA Translation: CAA61979.1
X91501 Genomic DNA Translation: CAA62800.1
CR456503 mRNA Translation: CAG30389.1
BC032721 mRNA Translation: AAH32721.1
BC039835 mRNA Translation: AAH39835.1
X75296 mRNA Translation: CAA53044.1 Different initiation.
CCDSiCCDS13759.1 [P54198-1]
PIRiI37465
S45344
RefSeqiNP_003316.3, NM_003325.3 [P54198-1]
UniGeneiHs.474206

Genome annotation databases

EnsembliENST00000263208; ENSP00000263208; ENSG00000100084 [P54198-1]
ENST00000340170; ENSP00000345350; ENSG00000100084 [P54198-2]
GeneIDi7290
KEGGihsa:7290
UCSCiuc002zpf.2 human [P54198-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81844 mRNA Translation: CAA57436.1 Different initiation.
X77633 mRNA Translation: CAA54721.1 Different initiation.
X89887 mRNA Translation: CAA61979.1
X91501 Genomic DNA Translation: CAA62800.1
CR456503 mRNA Translation: CAG30389.1
BC032721 mRNA Translation: AAH32721.1
BC039835 mRNA Translation: AAH39835.1
X75296 mRNA Translation: CAA53044.1 Different initiation.
CCDSiCCDS13759.1 [P54198-1]
PIRiI37465
S45344
RefSeqiNP_003316.3, NM_003325.3 [P54198-1]
UniGeneiHs.474206

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2I32X-ray2.70E/F425-472[»]
5YJEX-ray2.45A/B/C644-1017[»]
ProteinModelPortaliP54198
SMRiP54198
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113141, 39 interactors
CORUMiP54198
DIPiDIP-29240N
ELMiP54198
IntActiP54198, 19 interactors
MINTiP54198
STRINGi9606.ENSP00000263208

PTM databases

iPTMnetiP54198
PhosphoSitePlusiP54198

Polymorphism and mutation databases

BioMutaiHIRA
DMDMi88984228

Proteomic databases

EPDiP54198
MaxQBiP54198
PaxDbiP54198
PeptideAtlasiP54198
PRIDEiP54198
ProteomicsDBi56652
56653 [P54198-2]

Protocols and materials databases

DNASUi7290
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263208; ENSP00000263208; ENSG00000100084 [P54198-1]
ENST00000340170; ENSP00000345350; ENSG00000100084 [P54198-2]
GeneIDi7290
KEGGihsa:7290
UCSCiuc002zpf.2 human [P54198-1]

Organism-specific databases

CTDi7290
DisGeNETi7290
EuPathDBiHostDB:ENSG00000100084.14
GeneCardsiHIRA
HGNCiHGNC:4916 HIRA
HPAiCAB039243
CAB039244
HPA050714
HPA052902
MalaCardsiHIRA
MIMi600237 gene
neXtProtiNX_P54198
OpenTargetsiENSG00000100084
Orphaneti567 22q11.2 deletion syndrome
PharmGKBiPA29293
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0973 Eukaryota
ENOG410XP1H LUCA
GeneTreeiENSGT00550000074919
HOGENOMiHOG000007670
HOVERGENiHBG005969
InParanoidiP54198
KOiK11293
OMAiLLGPVHY
OrthoDBiEOG091G04F0
PhylomeDBiP54198
TreeFamiTF323161

Enzyme and pathway databases

ReactomeiR-HSA-2559584 Formation of Senescence-Associated Heterochromatin Foci (SAHF)
SignaLinkiP54198
SIGNORiP54198

Miscellaneous databases

ChiTaRSiHIRA human
EvolutionaryTraceiP54198
GeneWikiiHIRA
GenomeRNAii7290
PROiPR:P54198
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100084 Expressed in 205 organ(s), highest expression level in thyroid gland
CleanExiHS_HIRA
ExpressionAtlasiP54198 baseline and differential
GenevisibleiP54198 HS

Family and domain databases

Gene3Di2.130.10.10, 2 hits
InterProiView protein in InterPro
IPR031120 HIR1
IPR011494 Hira
IPR019015 HIRA_B_motif
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
PANTHERiPTHR13831 PTHR13831, 1 hit
PfamiView protein in Pfam
PF07569 Hira, 1 hit
PF09453 HIRA_B, 1 hit
PF00400 WD40, 4 hits
SMARTiView protein in SMART
SM00320 WD40, 7 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS00678 WD_REPEATS_1, 1 hit
PS50082 WD_REPEATS_2, 3 hits
PS50294 WD_REPEATS_REGION, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHIRA_HUMAN
AccessioniPrimary (citable) accession number: P54198
Secondary accession number(s): Q05BU9, Q8IXN2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 21, 2006
Last modified: September 12, 2018
This is version 180 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. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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