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UniProtKB - Q92619 (HMHA1_HUMAN)

Protein

Rho GTPase-activating protein 45

Gene

ARHGAP45

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

Functioni

Contains a GTPase activator for the Rho-type GTPases (RhoGAP) domain that would be able to negatively regulate the actin cytoskeleton as well as cell spreading. However, also contains N-terminally a BAR-domin which is able to play an autoinhibitory effect on this RhoGAP activity.1 Publication
Precursor of the histocompatibility antigen HA-1. More generally, minor histocompatibility antigens (mHags) refer to immunogenic peptide which, when complexed with MHC, can generate an immune response after recognition by specific T-cells. The peptides are derived from polymorphic intracellular proteins, which are cleaved by normal pathways of antigen processing. The binding of these peptides to MHC class I or class II molecules and its expression on the cell surface can stimulate T-cell responses and thereby trigger graft rejection or graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation from HLA-identical sibling donor. GVHD is a frequent complication after bone marrow transplantation (BMT), due to mismatch of minor histocompatibility antigen in HLA-matched sibling marrow transplants. Specifically, mismatching for mHag HA-1 which is recognized as immunodominant, is shown to be associated with the development of severe GVHD after HLA-identical BMT. HA-1 is presented to the cell surface by MHC class I HLA-A*0201, but also by other HLA-A alleles. This complex specifically elicits donor-cytotoxic T-lymphocyte (CTL) reactivity against hematologic malignancies after treatment by HLA-identical allogenic BMT. It induces cell recognition and lysis by CTL.4 Publications

Miscellaneous

Infusion of lymphocyte from mHag HA-1-negative donors results in a durable remission in mHag HA-1-positive patients with leukemia or multiple myeloma.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri702 – 747Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST46

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionGTPase activation
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-194840 Rho GTPase cycle
R-HSA-6798695 Neutrophil degranulation

Names & Taxonomyi

Protein namesi
Recommended name:
Rho GTPase-activating protein 45Imported
Cleaved into the following chain:
Minor histocompatibility antigen HA-1
Short name:
mHag HA-1
Gene namesi
Name:ARHGAP45Imported
Synonyms:HMHA1Imported, KIAA0223Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000180448.10
HGNCiHGNC:17102 ARHGAP45
MIMi601155 gene
neXtProtiNX_Q92619

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

Cell membrane, Cell projection, Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi23526
OpenTargetsiENSG00000180448
PharmGKBiPA128394633

Polymorphism and mutation databases

BioMutaiHMHA1
DMDMi187471158

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003303121 – 1136Rho GTPase-activating protein 45Add BLAST1136
PeptideiPRO_0000330313137 – 145Minor histocompatibility antigen HA-19

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei23PhosphoserineCombined sources1
Modified residuei25PhosphoserineCombined sources1
Modified residuei73PhosphoserineCombined sources1
Modified residuei93PhosphoserineCombined sources1
Modified residuei99PhosphoserineCombined sources1
Modified residuei569PhosphoserineCombined sources1
Modified residuei578PhosphoserineCombined sources1
Modified residuei592PhosphoserineCombined sources1
Modified residuei619PhosphoserineCombined sources1
Modified residuei949PhosphoserineCombined sources1
Modified residuei1027PhosphoserineBy similarity1
Modified residuei1030PhosphoserineBy similarity1
Modified residuei1032PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ92619
MaxQBiQ92619
PaxDbiQ92619
PeptideAtlasiQ92619
PRIDEiQ92619
ProteomicsDBi75372

PTM databases

iPTMnetiQ92619
PhosphoSitePlusiQ92619
SwissPalmiQ92619

Expressioni

Tissue specificityi

Expressed on cells of the hematopoietic lineage. Detected in dendritic cells and epidermal Langerhans cells. Expressed in peripheral blood mononuclear cells, in all leukemia/lymphoma cell lines. Detected also in some solid tumors and tissues such as cancerous and non-cancerous tissue.2 Publications

Gene expression databases

BgeeiENSG00000180448 Expressed in 185 organ(s), highest expression level in blood
ExpressionAtlasiQ92619 baseline and differential
GenevisibleiQ92619 HS

Organism-specific databases

HPAiHPA019816

Interactioni

Subunit structurei

HA-1 forms a complex with MHC class I HLA-A*0201.

Binary interactionsi

WithEntry#Exp.IntActNotes
RAC1P630003EBI-2825900,EBI-413628

Protein-protein interaction databases

BioGridi117072, 2 interactors
IntActiQ92619, 14 interactors
STRINGi9606.ENSP00000316772

Structurei

3D structure databases

ProteinModelPortaliQ92619
SMRiQ92619
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92619

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini269 – 539F-BARPROSITE-ProRule annotationAdd BLAST271
Domaini761 – 974Rho-GAPPROSITE-ProRule annotationAdd BLAST214

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili376 – 412Sequence analysisAdd BLAST37
Coiled coili440 – 499Sequence analysisAdd BLAST60

Domaini

Rho-GAP domain is able to regulate RhoGTPase activity, actin cytoskeleton and cell spreading. However N-terminally BAR domain plays an autoinhibitory role.1 Publication

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri702 – 747Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST46

Keywords - Domaini

Coiled coil, Zinc-finger

Phylogenomic databases

eggNOGiKOG1453 Eukaryota
ENOG410YM3I LUCA
GeneTreeiENSGT00930000150830
HOGENOMiHOG000112917
HOVERGENiHBG107979
InParanoidiQ92619
KOiK20644
PhylomeDBiQ92619
TreeFamiTF351450

Family and domain databases

CDDicd00029 C1, 1 hit
Gene3Di1.10.555.10, 1 hit
1.20.1270.60, 1 hit
InterProiView protein in InterPro
IPR027267 AH/BAR_dom_sf
IPR031160 F_BAR
IPR001060 FCH_dom
IPR002219 PE/DAG-bd
IPR008936 Rho_GTPase_activation_prot
IPR000198 RhoGAP_dom
PfamiView protein in Pfam
PF00620 RhoGAP, 1 hit
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00055 FCH, 1 hit
SM00324 RhoGAP, 1 hit
SUPFAMiSSF103657 SSF103657, 1 hit
SSF48350 SSF48350, 1 hit
PROSITEiView protein in PROSITE
PS51741 F_BAR, 1 hit
PS50238 RHOGAP, 1 hit
PS00479 ZF_DAG_PE_1, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

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

This entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q92619-1) [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
MFSRKKRELM KTPSISKKNR AGSPSPQPSG ELPRKDGADA VFPGPSLEPP 
        60         70         80         90        100
AGSSGVKATG TLKRPTSLSR HASAAGFPLS GAASWTLGRS HRSPLTAASP 
       110        120        130        140        150
GELPTEGAGP DVVEDISHLL ADVARFAEGL EKLKECVLRD DLLEARRPRA 
       160        170        180        190        200
HECLGEALRV MHQIISKYPL LNTVETLTAA GTLIAKVKAF HYESNNDLEK 
       210        220        230        240        250
QEFEKALETI AVAFSSTVSE FLMGEVDSST LLAVPPGDSS QSMESLYGPG 
       260        270        280        290        300
SEGTPPSLED CDAGCLPAEE VDVLLQRCEG GVDAALLYAK NMAKYMKDLI 
       310        320        330        340        350
SYLEKRTTLE MEFAKGLQKI AHNCRQSVMQ EPHMPLLSIY SLALEQDLEF 
       360        370        380        390        400
GHSMVQAVGT LQTQTFMQPL TLRRLEHEKR RKEIKEAWHR AQRKLQEAES 
       410        420        430        440        450
NLRKAKQGYV QRCEDHDKAR FLVAKAEEEQ AGSAPGAGST ATKTLDKRRR 
       460        470        480        490        500
LEEEAKNKAE EAMATYRTCV ADAKTQKQEL EDTKVTALRQ IQEVIRQSDQ 
       510        520        530        540        550
TIKSATISYY QMMHMQTAPL PVHFQMLCES SKLYDPGQQY ASHVRQLQRD 
       560        570        580        590        600
QEPDVHYDFE PHVSANAWSP VMRARKSSFN VSDVARPEAA GSPPEEGGCT 
       610        620        630        640        650
EGTPAKDHRA GRGHQVHKSW PLSISDSDSG LDPGPGAGDF KKFERTSSSG 
       660        670        680        690        700
TMSSTEELVD PDGGAGASAF EQADLNGMTP ELPVAVPSGP FRHEGLSKAA 
       710        720        730        740        750
RTHRLRKLRT PAKCRECNSY VYFQGAECEE CCLACHKKCL ETLAIQCGHK 
       760        770        780        790        800
KLQGRLQLFG QDFSHAARSA PDGVPFIVKK CVCEIERRAL RTKGIYRVNG 
       810        820        830        840        850
VKTRVEKLCQ AFENGKELVE LSQASPHDIS NVLKLYLRQL PEPLISFRLY 
       860        870        880        890        900
HELVGLAKDS LKAEAEAKAA SRGRQDGSES EAVAVALAGR LRELLRDLPP 
       910        920        930        940        950
ENRASLQYLL RHLRRIVEVE QDNKMTPGNL GIVFGPTLLR PRPTEATVSL 
       960        970        980        990       1000
SSLVDYPHQA RVIETLIVHY GLVFEEEPEE TPGGQDESSN QRAEVVVQVP 
      1010       1020       1030       1040       1050
YLEAGEAVVY PLQEAAADGC RESRVVSNDS DSDLEEASEL LSSSEASALG 
      1060       1070       1080       1090       1100
HLSFLEQQQS EASLEVASGS HSGSEEQLEA TAREDGDGDE DGPAQQLSGF 
      1110       1120       1130 
NTNQSNNVLQ APLPPMRLRG GRMTLGSCRE RQPEFV
Length:1,136
Mass (Da):124,614
Last modified:April 29, 2008 - v2
Checksum:i9536787B3B1EE16D
GO
Isoform 2 (identifier: Q92619-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-30: MFSRKKRELMKTPSISKKNRAGSPSPQPSG → MSRGQRVLKG...CPRDLPLPPE

Note: No experimental confirmation available.
Show »
Length:1,152
Mass (Da):126,497
Checksum:iE3144EE985E43A96
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
K7ES92K7ES92_HUMAN
Rho GTPase-activating protein 45
ARHGAP45
771Annotation score:
F5H1R4F5H1R4_HUMAN
Rho GTPase-activating protein 45
ARHGAP45
1,019Annotation score:
K7ES98K7ES98_HUMAN
Rho GTPase-activating protein 45
ARHGAP45
1,140Annotation score:
K7EM85K7EM85_HUMAN
Rho GTPase-activating protein 45
ARHGAP45
1,163Annotation score:
A0A087X1A3A0A087X1A3_HUMAN
Rho GTPase-activating protein 45
ARHGAP45
78Annotation score:
K7EQA4K7EQA4_HUMAN
Rho GTPase-activating protein 45
ARHGAP45
170Annotation score:
K7EM55K7EM55_HUMAN
Rho GTPase-activating protein 45
ARHGAP45
60Annotation score:

Sequence cautioni

The sequence BAA13212 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti648S → F in BAG62086 (PubMed:14702039).Curated1

Polymorphismi

The HA-1H allele is presented on the cell surface and recognized by CTL, whereas the HA-1R allele is poorly represented by HLA-A and non-immunogenic, although HA-1R allelic frequency is the highest (PubMed:9820595, PubMed:16399573).2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042693139R → H in allele HA-1H; induction of CTL recognition for epitope HA-1. 6 PublicationsCorresponds to variant dbSNP:rs1801284Ensembl.1
Natural variantiVAR_042694259E → D1 PublicationCorresponds to variant dbSNP:rs2074442Ensembl.1
Natural variantiVAR_042695439S → G1 PublicationCorresponds to variant dbSNP:rs7251797Ensembl.1
Natural variantiVAR_042696515M → I. Corresponds to variant dbSNP:rs36084354Ensembl.1
Natural variantiVAR_042697886A → P. Corresponds to variant dbSNP:rs34569196Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0447071 – 30MFSRK…PQPSG → MSRGQRVLKGLLGWVCTWTW AWRARLGARGCGLHVLCPRD LPLPPE in isoform 2. 1 PublicationAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF308066
, AF308045, AF308046, AF308047, AF308048, AF308049, AF308050, AF308051, AF308052, AF308053, AF308054, AF308055, AF308056, AF308057, AF308058, AF308059, AF308060, AF308061, AF308062, AF308063, AF308064, AF308065, AF311102 Genomic DNA Translation: AAN04658.1
D86976 mRNA Translation: BAA13212.1 Different initiation.
AK300341 mRNA Translation: BAG62086.1
AC004151 Genomic DNA Translation: AAC03237.1
AC011558 Genomic DNA No translation available.
AC093066 Genomic DNA No translation available.
CH471139 Genomic DNA Translation: EAW69551.1
BC048129 mRNA Translation: AAH48129.1
BC065223 mRNA Translation: AAH65223.1
AF207595 Genomic DNA Translation: AAG02014.1
AF207596 Genomic DNA Translation: AAG02015.1
AF207597 Genomic DNA Translation: AAG02016.1
AF236756 Genomic DNA Translation: AAF91292.1
CCDSiCCDS32863.1 [Q92619-1]
CCDS58637.1 [Q92619-2]
PIRiD59433
RefSeqiNP_001245257.1, NM_001258328.2 [Q92619-2]
NP_001269263.1, NM_001282334.1
NP_001269264.1, NM_001282335.1
NP_036424.2, NM_012292.4 [Q92619-1]
UniGeneiHs.465521
Hs.710732

Genome annotation databases

EnsembliENST00000313093; ENSP00000316772; ENSG00000180448 [Q92619-1]
ENST00000539243; ENSP00000439601; ENSG00000180448 [Q92619-2]
GeneIDi23526
KEGGihsa:23526
UCSCiuc002lqz.4 human [Q92619-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF308066
, AF308045, AF308046, AF308047, AF308048, AF308049, AF308050, AF308051, AF308052, AF308053, AF308054, AF308055, AF308056, AF308057, AF308058, AF308059, AF308060, AF308061, AF308062, AF308063, AF308064, AF308065, AF311102 Genomic DNA Translation: AAN04658.1
D86976 mRNA Translation: BAA13212.1 Different initiation.
AK300341 mRNA Translation: BAG62086.1
AC004151 Genomic DNA Translation: AAC03237.1
AC011558 Genomic DNA No translation available.
AC093066 Genomic DNA No translation available.
CH471139 Genomic DNA Translation: EAW69551.1
BC048129 mRNA Translation: AAH48129.1
BC065223 mRNA Translation: AAH65223.1
AF207595 Genomic DNA Translation: AAG02014.1
AF207596 Genomic DNA Translation: AAG02015.1
AF207597 Genomic DNA Translation: AAG02016.1
AF236756 Genomic DNA Translation: AAF91292.1
CCDSiCCDS32863.1 [Q92619-1]
CCDS58637.1 [Q92619-2]
PIRiD59433
RefSeqiNP_001245257.1, NM_001258328.2 [Q92619-2]
NP_001269263.1, NM_001282334.1
NP_001269264.1, NM_001282335.1
NP_036424.2, NM_012292.4 [Q92619-1]
UniGeneiHs.465521
Hs.710732

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3D25X-ray1.30C140-145[»]
3FT3X-ray1.95P137-145[»]
ProteinModelPortaliQ92619
SMRiQ92619
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117072, 2 interactors
IntActiQ92619, 14 interactors
STRINGi9606.ENSP00000316772

PTM databases

iPTMnetiQ92619
PhosphoSitePlusiQ92619
SwissPalmiQ92619

Polymorphism and mutation databases

BioMutaiHMHA1
DMDMi187471158

Proteomic databases

EPDiQ92619
MaxQBiQ92619
PaxDbiQ92619
PeptideAtlasiQ92619
PRIDEiQ92619
ProteomicsDBi75372

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000313093; ENSP00000316772; ENSG00000180448 [Q92619-1]
ENST00000539243; ENSP00000439601; ENSG00000180448 [Q92619-2]
GeneIDi23526
KEGGihsa:23526
UCSCiuc002lqz.4 human [Q92619-1]

Organism-specific databases

CTDi23526
DisGeNETi23526
EuPathDBiHostDB:ENSG00000180448.10
GeneCardsiARHGAP45
H-InvDBiHIX0014570
HGNCiHGNC:17102 ARHGAP45
HPAiHPA019816
MIMi601155 gene
neXtProtiNX_Q92619
OpenTargetsiENSG00000180448
PharmGKBiPA128394633
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1453 Eukaryota
ENOG410YM3I LUCA
GeneTreeiENSGT00930000150830
HOGENOMiHOG000112917
HOVERGENiHBG107979
InParanoidiQ92619
KOiK20644
PhylomeDBiQ92619
TreeFamiTF351450

Enzyme and pathway databases

ReactomeiR-HSA-194840 Rho GTPase cycle
R-HSA-6798695 Neutrophil degranulation

Miscellaneous databases

ChiTaRSiARHGAP45 human
EvolutionaryTraceiQ92619
GeneWikiiHMHA1
GenomeRNAii23526
PROiPR:Q92619
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000180448 Expressed in 185 organ(s), highest expression level in blood
ExpressionAtlasiQ92619 baseline and differential
GenevisibleiQ92619 HS

Family and domain databases

CDDicd00029 C1, 1 hit
Gene3Di1.10.555.10, 1 hit
1.20.1270.60, 1 hit
InterProiView protein in InterPro
IPR027267 AH/BAR_dom_sf
IPR031160 F_BAR
IPR001060 FCH_dom
IPR002219 PE/DAG-bd
IPR008936 Rho_GTPase_activation_prot
IPR000198 RhoGAP_dom
PfamiView protein in Pfam
PF00620 RhoGAP, 1 hit
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00055 FCH, 1 hit
SM00324 RhoGAP, 1 hit
SUPFAMiSSF103657 SSF103657, 1 hit
SSF48350 SSF48350, 1 hit
PROSITEiView protein in PROSITE
PS51741 F_BAR, 1 hit
PS50238 RHOGAP, 1 hit
PS00479 ZF_DAG_PE_1, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHMHA1_HUMAN
AccessioniPrimary (citable) accession number: Q92619
Secondary accession number(s): B4DTS4
, F6QP70, Q6P189, Q7LE26, Q86WS1, Q8HX84, Q9GJN9, Q9GJP0, Q9GJP1, Q9MY24
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 29, 2008
Last sequence update: April 29, 2008
Last modified: November 7, 2018
This is version 147 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 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. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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