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Protein

Rho GTPase-activating protein 45

Gene

ARHGAP45

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Biological processi

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:
Gene namesi
Name:ARHGAP45Imported
Synonyms:HMHA1Imported, KIAA0223Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000180448.10.
HGNCiHGNC:17102. ARHGAP45.

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.

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.
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

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...

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.
GeneTreeiENSGT00900000140777.
HOGENOMiHOG000112917.
HOVERGENiHBG107979.
InParanoidiQ92619.
KOiK20644.
PhylomeDBiQ92619.
TreeFamiTF351450.

Family and domain databases

CDDicd00029. C1. 1 hit.
Gene3Di1.10.555.10. 2 hits.
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

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

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

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 22, 2017
This is version 143 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 chromosome 19
    Human chromosome 19: 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references