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Protein

G-protein-signaling modulator 2

Gene

GPSM2

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

Functioni

Plays an important role in mitotic spindle pole organization via its interaction with NUMA1 (PubMed:11781568, PubMed:15632202, PubMed:21816348). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364). Plays a role in metaphase spindle orientation (PubMed:22327364). Plays also an important role in asymmetric cell divisions (PubMed:21816348). Has guanine nucleotide dissociation inhibitor (GDI) activity towards G(i) alpha proteins, such as GNAI1 and GNAI3, and thereby regulates their activity (By similarity).By similarity4 Publications

Miscellaneous

Dysfunction of LGN is associated with the phenotype of multiple micronuclei due to chromosomal mis-segregation and defect in cell division through mis-localization of mitotic spindle regulator protein NUMA1.Curated

Caution

It is uncertain whether Met-1 or Met-8 is the initiator.Curated
Mutations in GPSM2 have been identified in people with profound congenital non-syndromic deafness designated as DFNB82 (PubMed:20602914). Subsequent brain imaging of these individuals has revealed frontal polymicrogyria, abnormal corpus callosum, and gray matter heterotopia, consistent with a diagnosis of Chudley-McCullough syndrome (PubMed:22578326).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei608GDP; shared with dimeric partnerBy similarity1
Binding sitei613GDP; shared with dimeric partnerBy similarity1
Binding sitei642GDP; shared with dimeric partnerBy similarity1
Binding sitei647GDP; shared with dimeric partnerBy similarity1

GO - Molecular functioni

  • dynein complex binding Source: UniProtKB
  • GDP-dissociation inhibitor activity Source: UniProtKB
  • G-protein alpha-subunit binding Source: Ensembl
  • identical protein binding Source: IntAct
  • nucleotide binding Source: UniProtKB-KW
  • protein C-terminus binding Source: UniProtKB
  • protein domain specific binding Source: UniProtKB
  • protein self-association Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processCell cycle, Cell division, Mitosis, Transport
LigandNucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-418594 G alpha (i) signalling events
SIGNORiP81274

Names & Taxonomyi

Protein namesi
Recommended name:
G-protein-signaling modulator 2
Alternative name(s):
Mosaic protein LGN1 Publication
Gene namesi
Name:GPSM2
Synonyms:LGN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000121957.12
HGNCiHGNC:29501 GPSM2
MIMi609245 gene
neXtProtiNX_P81274

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, Cytoplasm, Cytoskeleton, Membrane

Pathology & Biotechi

Involvement in diseasei

Chudley-McCullough syndrome (CMCS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive neurologic disorder characterized by early-onset sensorineural deafness and specific brain anomalies on MRI, including hypoplasia of the corpus callosum, enlarged cysterna magna with mild focal cerebellar dysplasia, and nodular heterotopia. Some patients have hydrocephalus. Psychomotor development is normal.
See also OMIM:604213

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi228R → A: Abolishes location at mitotic spindle poles; when associated with A-243. 1 Publication1
Mutagenesisi228R → E: Strongly reduces interaction with INSC. Abolishes interaction with INSC; when associated with R-290. 1 Publication1
Mutagenesisi243R → A: Abolishes location at mitotic spindle poles; when associated with A-228. 1 Publication1
Mutagenesisi290N → R: Abolishes interaction with INSC; when associated with E-228. 1 Publication1

Keywords - Diseasei

Deafness

Organism-specific databases

DisGeNETi29899
MalaCardsiGPSM2
MIMi604213 phenotype
OpenTargetsiENSG00000121957
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
314597 Chudley-McCullough syndrome
PharmGKBiPA134993615

Polymorphism and mutation databases

BioMutaiGPSM2
DMDMi294862507

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001063581 – 684G-protein-signaling modulator 2Add BLAST684

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei132Phosphoserine; by PKGSequence analysis1
Modified residuei352Phosphoserine; by PKGSequence analysis1
Modified residuei408PhosphoserineCombined sources1
Modified residuei483PhosphoserineCombined sources1
Modified residuei486PhosphothreonineCombined sources1
Modified residuei501Phosphoserine; by PKCSequence analysis1
Modified residuei541PhosphoserineCombined sources1
Modified residuei565PhosphoserineCombined sources1
Modified residuei607Phosphoserine; by PKGSequence analysis1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP81274
MaxQBiP81274
PaxDbiP81274
PeptideAtlasiP81274
PRIDEiP81274
ProteomicsDBi57693

PTM databases

iPTMnetiP81274
PhosphoSitePlusiP81274

Expressioni

Tissue specificityi

Ubiquitously expressed.

Gene expression databases

BgeeiENSG00000121957 Expressed in 222 organ(s), highest expression level in tibia
CleanExiHS_GPSM2
ExpressionAtlasiP81274 baseline and differential
GenevisibleiP81274 HS

Organism-specific databases

HPAiCAB018962
HPA007327
HPA008408

Interactioni

Subunit structurei

Interacts with the dynein-dynactin complex; this interaction is inhibited in a PLK1-dependent manner (PubMed:22327364). Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1 (PubMed:26766442). Interacts with LLGL2 (PubMed:15632202). Interacts (via TPR repeat region) with INSC/inscuteable (PubMed:16458856, PubMed:22074847). Interacts (via TPR repeat region) with NUMA1 (via C-terminus); this interaction is direct, inhibited in a PLK1-dependent manner, prevents the binding of NUMA1 with SPAG5 and promotes spindle pole organization (PubMed:11781568, PubMed:22327364, PubMed:27462074). INSC and NUMA1 compete for the same binding site, but INSC has higher affinity and can displace NUMA1 (in vitro) (PubMed:22074847). Interacts with GNAI2 (PubMed:8973305). Interacts (via GoLoco domains) with the GDP-bound form of GNAI1 and GNAI3; has much lower affinity for the GTP-bound form. Interaction with GDP-bound GNAI3 strongly enhances the affinity for NUMA1 (By similarity). Interacts (via TPR repeat region) with FRMPD1 (PubMed:22074847). INSC and FRMPD1 compete for the same binding site, but INSC has higher affinity and can displace FRMPD1 (in vitro) (By similarity). Interacts (via TPR repeat region) with FRMPD4 (PubMed:22074847, PubMed:25664792). Identified in a complex with INSC and F2RL2/Par3 (PubMed:16458856).By similarity9 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi118949, 15 interactors
CORUMiP81274
DIPiDIP-399N
IntActiP81274, 18 interactors
MINTiP81274
STRINGi9606.ENSP00000264126

Structurei

Secondary structure

1684
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP81274
SMRiP81274
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati24 – 57TPR 1Add BLAST34
Repeati62 – 95TPR 2Add BLAST34
Repeati102 – 135TPR 3Add BLAST34
Repeati142 – 184TPR 4Add BLAST43
Repeati202 – 235TPR 5Add BLAST34
Repeati242 – 275TPR 6Add BLAST34
Repeati282 – 315TPR 7Add BLAST34
Repeati322 – 355TPR 8Add BLAST34
Domaini489 – 511GoLoco 1PROSITE-ProRule annotationAdd BLAST23
Domaini544 – 566GoLoco 2PROSITE-ProRule annotationAdd BLAST23
Domaini594 – 616GoLoco 3PROSITE-ProRule annotationAdd BLAST23
Domaini628 – 650GoLoco 4PROSITE-ProRule annotationAdd BLAST23

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni22 – 357Important for interaction with NUMA1; INSC and FRMPD1By similarityAdd BLAST336

Sequence similaritiesi

Belongs to the GPSM family.Curated

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG1130 Eukaryota
ENOG410XP6N LUCA
GeneTreeiENSGT00530000063126
HOGENOMiHOG000231543
HOVERGENiHBG051823
InParanoidiP81274
KOiK15837
OMAiMLKTPSV
OrthoDBiEOG091G04C9
PhylomeDBiP81274
TreeFamiTF328344

Family and domain databases

Gene3Di1.25.40.10, 3 hits
InterProiView protein in InterPro
IPR003109 GoLoco_motif
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR019734 TPR_repeat
PfamiView protein in Pfam
PF02188 GoLoco, 4 hits
PF13176 TPR_7, 2 hits
PF13181 TPR_8, 1 hit
SMARTiView protein in SMART
SM00390 GoLoco, 4 hits
SM00028 TPR, 7 hits
SUPFAMiSSF48452 SSF48452, 2 hits
PROSITEiView protein in PROSITE
PS50877 GOLOCO, 4 hits
PS50005 TPR, 6 hits
PS50293 TPR_REGION, 2 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 8 potential isoforms that are computationally mapped.Show allAlign All

P81274-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MEENLISMRE DHSFHVRYRM EASCLELALE GERLCKSGDC RAGVSFFEAA
60 70 80 90 100
VQVGTEDLKT LSAIYSQLGN AYFYLHDYAK ALEYHHHDLT LARTIGDQLG
110 120 130 140 150
EAKASGNLGN TLKVLGNFDE AIVCCQRHLD ISRELNDKVG EARALYNLGN
160 170 180 190 200
VYHAKGKSFG CPGPQDVGEF PEEVRDALQA AVDFYEENLS LVTALGDRAA
210 220 230 240 250
QGRAFGNLGN THYLLGNFRD AVIAHEQRLL IAKEFGDKAA ERRAYSNLGN
260 270 280 290 300
AYIFLGEFET ASEYYKKTLL LARQLKDRAV EAQSCYSLGN TYTLLQDYEK
310 320 330 340 350
AIDYHLKHLA IAQELNDRIG EGRACWSLGN AYTALGNHDQ AMHFAEKHLE
360 370 380 390 400
ISREVGDKSG ELTARLNLSD LQMVLGLSYS TNNSIMSENT EIDSSLNGVR
410 420 430 440 450
PKLGRRHSME NMELMKLTPE KVQNWNSEIL AKQKPLIAKP SAKLLFVNRL
460 470 480 490 500
KGKKYKTNSS TKVLQDASNS IDHRIPNSQR KISADTIGDE GFFDLLSRFQ
510 520 530 540 550
SNRMDDQRCC LQEKNCHTAS TTTSSTPPKM MLKTSSVPVV SPNTDEFLDL
560 570 580 590 600
LASSQSRRLD DQRASFSNLP GLRLTQNSQS VLSHLMTNDN KEADEDFFDI
610 620 630 640 650
LVKCQGSRLD DQRCAPPPAT TKGPTVPDED FFSLILRSQG KRMDEQRVLL
660 670 680
QRDQNRDTDF GLKDFLQNNA LLEFKNSGKK SADH
Length:684
Mass (Da):76,662
Last modified:April 20, 2010 - v3
Checksum:iD007A4765F57CB90
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5T1N9Q5T1N9_HUMAN
G-protein-signaling modulator 2
GPSM2
213Annotation score:
H0Y4A4H0Y4A4_HUMAN
G-protein-signaling modulator 2
GPSM2
217Annotation score:
A0A2R8Y6E3A0A2R8Y6E3_HUMAN
G-protein-signaling modulator 2
GPSM2
311Annotation score:
B0QZC9B0QZC9_HUMAN
G-protein-signaling modulator 2
GPSM2
52Annotation score:
B0QZD0B0QZD0_HUMAN
G-protein-signaling modulator 2
GPSM2
75Annotation score:
A0A2R8YCX1A0A2R8YCX1_HUMAN
G-protein-signaling modulator 2
GPSM2
228Annotation score:
A0A2R8Y896A0A2R8Y896_HUMAN
G-protein-signaling modulator 2
GPSM2
83Annotation score:
A0A2R8Y673A0A2R8Y673_HUMAN
G-protein-signaling modulator 2
GPSM2
93Annotation score:

Sequence cautioni

The sequence AAB40385 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAH27732 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti400R → L in AAB40385 (PubMed:8973305).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U54999 mRNA Translation: AAB40385.1 Different initiation.
AB445462 mRNA Translation: BAH84760.1
AL449266 Genomic DNA No translation available.
CH471122 Genomic DNA Translation: EAW56340.1
BC027732 mRNA Translation: AAH27732.1 Different initiation.
AY136740 mRNA Translation: AAN01266.1
CR456786 mRNA Translation: CAG33067.1
CCDSiCCDS792.2
PIRiJC5334 G02540
RefSeqiNP_001307967.1, NM_001321038.1
NP_001307968.1, NM_001321039.1
NP_037428.3, NM_013296.4
XP_011539603.1, XM_011541301.2
XP_011539604.1, XM_011541302.2
XP_016856586.1, XM_017001097.1
XP_016856587.1, XM_017001098.1
UniGeneiHs.584901
Hs.658489

Genome annotation databases

EnsembliENST00000264126; ENSP00000264126; ENSG00000121957
ENST00000406462; ENSP00000385510; ENSG00000121957
ENST00000642355; ENSP00000496104; ENSG00000121957
GeneIDi29899
KEGGihsa:29899
UCSCiuc010ovc.3 human

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U54999 mRNA Translation: AAB40385.1 Different initiation.
AB445462 mRNA Translation: BAH84760.1
AL449266 Genomic DNA No translation available.
CH471122 Genomic DNA Translation: EAW56340.1
BC027732 mRNA Translation: AAH27732.1 Different initiation.
AY136740 mRNA Translation: AAN01266.1
CR456786 mRNA Translation: CAG33067.1
CCDSiCCDS792.2
PIRiJC5334 G02540
RefSeqiNP_001307967.1, NM_001321038.1
NP_001307968.1, NM_001321039.1
NP_037428.3, NM_013296.4
XP_011539603.1, XM_011541301.2
XP_011539604.1, XM_011541302.2
XP_016856586.1, XM_017001097.1
XP_016856587.1, XM_017001098.1
UniGeneiHs.584901
Hs.658489

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3SF4X-ray2.60A/B/C20-421[»]
4WNDX-ray1.50A20-421[»]
4WNEX-ray2.00A20-421[»]
4WNFX-ray2.90A20-421[»]
4WNGX-ray2.11A20-421[»]
5A6CX-ray2.90A/B22-357[»]
ProteinModelPortaliP81274
SMRiP81274
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118949, 15 interactors
CORUMiP81274
DIPiDIP-399N
IntActiP81274, 18 interactors
MINTiP81274
STRINGi9606.ENSP00000264126

PTM databases

iPTMnetiP81274
PhosphoSitePlusiP81274

Polymorphism and mutation databases

BioMutaiGPSM2
DMDMi294862507

Proteomic databases

EPDiP81274
MaxQBiP81274
PaxDbiP81274
PeptideAtlasiP81274
PRIDEiP81274
ProteomicsDBi57693

Protocols and materials databases

DNASUi29899
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264126; ENSP00000264126; ENSG00000121957
ENST00000406462; ENSP00000385510; ENSG00000121957
ENST00000642355; ENSP00000496104; ENSG00000121957
GeneIDi29899
KEGGihsa:29899
UCSCiuc010ovc.3 human

Organism-specific databases

CTDi29899
DisGeNETi29899
EuPathDBiHostDB:ENSG00000121957.12
GeneCardsiGPSM2
HGNCiHGNC:29501 GPSM2
HPAiCAB018962
HPA007327
HPA008408
MalaCardsiGPSM2
MIMi604213 phenotype
609245 gene
neXtProtiNX_P81274
OpenTargetsiENSG00000121957
Orphaneti90636 Autosomal recessive non-syndromic sensorineural deafness type DFNB
314597 Chudley-McCullough syndrome
PharmGKBiPA134993615
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1130 Eukaryota
ENOG410XP6N LUCA
GeneTreeiENSGT00530000063126
HOGENOMiHOG000231543
HOVERGENiHBG051823
InParanoidiP81274
KOiK15837
OMAiMLKTPSV
OrthoDBiEOG091G04C9
PhylomeDBiP81274
TreeFamiTF328344

Enzyme and pathway databases

ReactomeiR-HSA-418594 G alpha (i) signalling events
SIGNORiP81274

Miscellaneous databases

GeneWikiiGPSM2
GenomeRNAii29899
PROiPR:P81274
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121957 Expressed in 222 organ(s), highest expression level in tibia
CleanExiHS_GPSM2
ExpressionAtlasiP81274 baseline and differential
GenevisibleiP81274 HS

Family and domain databases

Gene3Di1.25.40.10, 3 hits
InterProiView protein in InterPro
IPR003109 GoLoco_motif
IPR013026 TPR-contain_dom
IPR011990 TPR-like_helical_dom_sf
IPR019734 TPR_repeat
PfamiView protein in Pfam
PF02188 GoLoco, 4 hits
PF13176 TPR_7, 2 hits
PF13181 TPR_8, 1 hit
SMARTiView protein in SMART
SM00390 GoLoco, 4 hits
SM00028 TPR, 7 hits
SUPFAMiSSF48452 SSF48452, 2 hits
PROSITEiView protein in PROSITE
PS50877 GOLOCO, 4 hits
PS50005 TPR, 6 hits
PS50293 TPR_REGION, 2 hits
ProtoNetiSearch...

Entry informationi

Entry nameiGPSM2_HUMAN
AccessioniPrimary (citable) accession number: P81274
Secondary accession number(s): Q5T1N8, Q6IBL7, Q8N0Z5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: April 20, 2010
Last modified: November 7, 2018
This is version 191 of the entry and version 3 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. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  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
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