UniProtKB - Q92619 (HMHA1_HUMAN)
Protein
Rho GTPase-activating protein 45
Gene
ARHGAP45
Organism
Homo sapiens (Human)
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 702 – 747 | Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST | 46 |
GO - Molecular functioni
- GTPase activator activity Source: GO_Central
- metal ion binding Source: UniProtKB-KW
GO - Biological processi
- activation of GTPase activity Source: GO_Central
- intracellular signal transduction Source: InterPro
- neutrophil degranulation Source: Reactome
- regulation of small GTPase mediated signal transduction Source: Reactome
Keywordsi
Molecular function | GTPase activation |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q92619 |
Reactomei | R-HSA-194840, Rho GTPase cycle R-HSA-6798695, Neutrophil degranulation |
Names & Taxonomyi
Protein namesi | Recommended name: Rho GTPase-activating protein 45ImportedCleaved into the following chain: |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17102, ARHGAP45 |
MIMi | 601155, gene |
neXtProti | NX_Q92619 |
VEuPathDBi | HostDB:ENSG00000180448.10 |
Subcellular locationi
Plasma membrane
- ruffle membrane 1 Publication
Other locations
- Cytoplasm 1 Publication
Cytosol
- cytosol Source: Reactome
Extracellular region or secreted
- extracellular region Source: Reactome
Lysosome
- azurophil granule lumen Source: Reactome
Plasma Membrane
- ruffle membrane Source: UniProtKB-SubCell
Other locations
- membrane Source: UniProtKB
- secretory granule lumen Source: Reactome
Keywords - Cellular componenti
Cell membrane, Cell projection, Cytoplasm, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 23526 |
NIAGADSi | ENSG00000180448 |
OpenTargetsi | ENSG00000180448 |
PharmGKBi | PA128394633 |
Miscellaneous databases
Pharosi | Q92619, Tbio |
Genetic variation databases
BioMutai | ARHGAP45 |
DMDMi | 187471158 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000330312 | 1 – 1136 | Rho GTPase-activating protein 45Add BLAST | 1136 | |
PeptideiPRO_0000330313 | 137 – 145 | Minor histocompatibility antigen HA-1 | 9 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 23 | PhosphoserineCombined sources | 1 | |
Modified residuei | 25 | PhosphoserineCombined sources | 1 | |
Modified residuei | 73 | PhosphoserineCombined sources | 1 | |
Modified residuei | 93 | PhosphoserineCombined sources | 1 | |
Modified residuei | 99 | PhosphoserineCombined sources | 1 | |
Modified residuei | 569 | PhosphoserineCombined sources | 1 | |
Modified residuei | 578 | PhosphoserineCombined sources | 1 | |
Modified residuei | 592 | PhosphoserineCombined sources | 1 | |
Modified residuei | 619 | PhosphoserineCombined sources | 1 | |
Modified residuei | 949 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1027 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1030 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1032 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q92619 |
jPOSTi | Q92619 |
MassIVEi | Q92619 |
MaxQBi | Q92619 |
PaxDbi | Q92619 |
PeptideAtlasi | Q92619 |
PRIDEi | Q92619 |
ProteomicsDBi | 27852 75372 [Q92619-1] |
PTM databases
GlyGeni | Q92619, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q92619 |
PhosphoSitePlusi | Q92619 |
SwissPalmi | Q92619 |
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
Bgeei | ENSG00000180448, Expressed in granulocyte and 200 other tissues |
ExpressionAtlasi | Q92619, baseline and differential |
Genevisiblei | Q92619, HS |
Organism-specific databases
HPAi | ENSG00000180448, Group enriched (blood, bone marrow, intestine, lung, lymphoid tissue) |
Interactioni
Subunit structurei
HA-1 forms a complex with MHC class I HLA-A*0201.
Binary interactionsi
Hide detailsQ92619
Protein-protein interaction databases
BioGRIDi | 117072, 13 interactors |
IntActi | Q92619, 20 interactors |
STRINGi | 9606.ENSP00000439601 |
Miscellaneous databases
RNActi | Q92619, protein |
Structurei
3D structure databases
SMRi | Q92619 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q92619 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 269 – 539 | F-BARPROSITE-ProRule annotationAdd BLAST | 271 | |
Domaini | 761 – 974 | Rho-GAPPROSITE-ProRule annotationAdd BLAST | 214 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 376 – 412 | Sequence analysisAdd BLAST | 37 | |
Coiled coili | 440 – 499 | Sequence analysisAdd BLAST | 60 |
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 702 – 747 | Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST | 46 |
Keywords - Domaini
Coiled coil, Zinc-fingerPhylogenomic databases
eggNOGi | KOG1453, Eukaryota |
GeneTreei | ENSGT00950000183110 |
HOGENOMi | CLU_006236_0_1_1 |
InParanoidi | Q92619 |
OrthoDBi | 1300981at2759 |
PhylomeDBi | Q92619 |
TreeFami | TF351450 |
Family and domain databases
CDDi | cd00029, C1, 1 hit |
Gene3Di | 1.10.555.10, 1 hit 1.20.1270.60, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00620, RhoGAP, 1 hit |
SMARTi | View protein in SMART SM00109, C1, 1 hit SM00055, FCH, 1 hit SM00324, RhoGAP, 1 hit |
SUPFAMi | SSF103657, SSF103657, 1 hit SSF48350, SSF48350, 1 hit |
PROSITEi | View 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 |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis 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 sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF5H1R4 | F5H1R4_HUMAN | Rho GTPase-activating protein 45 | ARHGAP45 | 1,019 | Annotation score: | ||
K7ES92 | K7ES92_HUMAN | Rho GTPase-activating protein 45 | ARHGAP45 | 771 | Annotation score: | ||
K7ES98 | K7ES98_HUMAN | Rho GTPase-activating protein 45 | ARHGAP45 | 1,140 | Annotation score: | ||
K7EM85 | K7EM85_HUMAN | Rho GTPase-activating protein 45 | ARHGAP45 | 1,163 | Annotation score: | ||
A0A087X1A3 | A0A087X1A3_HUMAN | Rho GTPase-activating protein 45 | ARHGAP45 | 78 | Annotation score: | ||
K7EQA4 | K7EQA4_HUMAN | Rho GTPase-activating protein 45 | ARHGAP45 | 170 | Annotation score: | ||
K7EM55 | K7EM55_HUMAN | Rho GTPase-activating protein 45 | ARHGAP45 | 60 | Annotation score: |
Sequence cautioni
The sequence BAA13212 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 648 | S → F in BAG62086 (PubMed:14702039).Curated | 1 |
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_042693 | 139 | R → H in allele HA-1H; induction of CTL recognition for epitope HA-1. 6 PublicationsCorresponds to variant dbSNP:rs1801284Ensembl. | 1 | |
Natural variantiVAR_042694 | 259 | E → D1 PublicationCorresponds to variant dbSNP:rs2074442Ensembl. | 1 | |
Natural variantiVAR_042695 | 439 | S → G1 PublicationCorresponds to variant dbSNP:rs7251797Ensembl. | 1 | |
Natural variantiVAR_042696 | 515 | M → I. Corresponds to variant dbSNP:rs36084354Ensembl. | 1 | |
Natural variantiVAR_042697 | 886 | A → P. Corresponds to variant dbSNP:rs34569196Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_044707 | 1 – 30 | MFSRK…PQPSG → MSRGQRVLKGLLGWVCTWTW AWRARLGARGCGLHVLCPRD LPLPPE in isoform 2. 1 PublicationAdd BLAST | 30 |
Sequence databases
Genome annotation databases
Ensembli | ENST00000313093; ENSP00000316772; ENSG00000180448 [Q92619-1] ENST00000539243; ENSP00000439601; ENSG00000180448 [Q92619-2] |
GeneIDi | 23526 |
KEGGi | hsa:23526 |
UCSCi | uc002lqz.4, human [Q92619-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3D25 | X-ray | 1.30 | C | 140-145 | [»] | |
3FT3 | X-ray | 1.95 | P | 137-145 | [»] | |
SMRi | Q92619 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 117072, 13 interactors |
IntActi | Q92619, 20 interactors |
STRINGi | 9606.ENSP00000439601 |
PTM databases
GlyGeni | Q92619, 1 site, 1 O-linked glycan (1 site) |
iPTMneti | Q92619 |
PhosphoSitePlusi | Q92619 |
SwissPalmi | Q92619 |
Genetic variation databases
BioMutai | ARHGAP45 |
DMDMi | 187471158 |
Proteomic databases
EPDi | Q92619 |
jPOSTi | Q92619 |
MassIVEi | Q92619 |
MaxQBi | Q92619 |
PaxDbi | Q92619 |
PeptideAtlasi | Q92619 |
PRIDEi | Q92619 |
ProteomicsDBi | 27852 75372 [Q92619-1] |
Protocols and materials databases
Antibodypediai | 10356, 173 antibodies |
Genome annotation databases
Ensembli | ENST00000313093; ENSP00000316772; ENSG00000180448 [Q92619-1] ENST00000539243; ENSP00000439601; ENSG00000180448 [Q92619-2] |
GeneIDi | 23526 |
KEGGi | hsa:23526 |
UCSCi | uc002lqz.4, human [Q92619-1] |
Organism-specific databases
CTDi | 23526 |
DisGeNETi | 23526 |
GeneCardsi | ARHGAP45 |
HGNCi | HGNC:17102, ARHGAP45 |
HPAi | ENSG00000180448, Group enriched (blood, bone marrow, intestine, lung, lymphoid tissue) |
MIMi | 601155, gene |
neXtProti | NX_Q92619 |
NIAGADSi | ENSG00000180448 |
OpenTargetsi | ENSG00000180448 |
PharmGKBi | PA128394633 |
VEuPathDBi | HostDB:ENSG00000180448.10 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1453, Eukaryota |
GeneTreei | ENSGT00950000183110 |
HOGENOMi | CLU_006236_0_1_1 |
InParanoidi | Q92619 |
OrthoDBi | 1300981at2759 |
PhylomeDBi | Q92619 |
TreeFami | TF351450 |
Enzyme and pathway databases
PathwayCommonsi | Q92619 |
Reactomei | R-HSA-194840, Rho GTPase cycle R-HSA-6798695, Neutrophil degranulation |
Miscellaneous databases
BioGRID-ORCSi | 23526, 23 hits in 875 CRISPR screens |
ChiTaRSi | ARHGAP45, human |
EvolutionaryTracei | Q92619 |
GeneWikii | HMHA1 |
GenomeRNAii | 23526 |
Pharosi | Q92619, Tbio |
PROi | PR:Q92619 |
RNActi | Q92619, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000180448, Expressed in granulocyte and 200 other tissues |
ExpressionAtlasi | Q92619, baseline and differential |
Genevisiblei | Q92619, HS |
Family and domain databases
CDDi | cd00029, C1, 1 hit |
Gene3Di | 1.10.555.10, 1 hit 1.20.1270.60, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00620, RhoGAP, 1 hit |
SMARTi | View protein in SMART SM00109, C1, 1 hit SM00055, FCH, 1 hit SM00324, RhoGAP, 1 hit |
SUPFAMi | SSF103657, SSF103657, 1 hit SSF48350, SSF48350, 1 hit |
PROSITEi | View 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HMHA1_HUMAN | |
Accessioni | Q92619Primary (citable) accession number: Q92619 Secondary accession number(s): B4DTS4 Q9MY24 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | April 29, 2008 |
Last sequence update: | April 29, 2008 | |
Last modified: | February 10, 2021 | |
This is version 162 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 19
Human chromosome 19: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references