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Protein

G-protein-signaling modulator 2

Gene

GPSM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays an important role in mitotic spindle pole organization via its interaction with NUMA1 (PubMed:15632202, PubMed:21816348). Plays 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 similarity2 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

  • GDP-dissociation inhibitor activity Source: UniProtKB
  • identical protein binding Source: IntAct
  • nucleotide binding Source: UniProtKB-KW

GO - Biological processi

  • establishment of mitotic spindle orientation Source: Ensembl
  • G-protein coupled receptor signaling pathway Source: ProtInc
  • lung epithelial cell differentiation Source: Ensembl
  • maintenance of centrosome location Source: UniProtKB
  • mitotic spindle organization Source: UniProtKB
Complete GO annotation...

Keywords - Ligandi

Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000121957-MONOMER.
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

HGNCiHGNC:29501. GPSM2.

Subcellular locationi

GO - Cellular componenti

  • apical part of cell Source: Ensembl
  • cell cortex Source: UniProtKB
  • cytoplasm Source: HPA
  • spindle pole Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton

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.

PTM databases

iPTMnetiP81274.
PhosphoSitePlusiP81274.

Expressioni

Tissue specificityi

Ubiquitously expressed.

Gene expression databases

BgeeiENSG00000121957.
CleanExiHS_GPSM2.
ExpressionAtlasiP81274. baseline and differential.
GenevisibleiP81274. HS.

Organism-specific databases

HPAiCAB018962.
HPA007327.
HPA008408.

Interactioni

Subunit structurei

Interacts with LLGL2 (PubMed:15632202). Interacts (via TPR repeat region) with INSC/inscuteable (PubMed:16458856, PubMed:22074847). Interacts (via TPR repeat region) with NUMA1. 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 similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself7EBI-618655,EBI-618655
GNAI1P630963EBI-618655,EBI-618639
NUMA1Q149806EBI-618655,EBI-521611

GO - Molecular functioni

  • identical protein binding Source: IntAct

Protein-protein interaction databases

BioGridi118949. 13 interactors.
DIPiDIP-399N.
IntActiP81274. 16 interactors.
MINTiMINT-3023522.
STRINGi9606.ENSP00000264126.

Structurei

Secondary structure

1684
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi24 – 36Combined sources13
Helixi40 – 53Combined sources14
Helixi58 – 74Combined sources17
Helixi78 – 94Combined sources17
Helixi98 – 115Combined sources18
Helixi118 – 134Combined sources17
Helixi138 – 158Combined sources21
Helixi165 – 168Combined sources4
Helixi172 – 194Combined sources23
Helixi198 – 215Combined sources18
Helixi218 – 234Combined sources17
Helixi238 – 254Combined sources17
Helixi258 – 272Combined sources15
Helixi278 – 294Combined sources17
Helixi298 – 314Combined sources17
Helixi318 – 334Combined sources17
Helixi338 – 354Combined sources17
Helixi358 – 376Combined sources19

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...

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
Contains 4 GoLoco domains.PROSITE-ProRule annotation
Contains 8 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di1.25.40.10. 2 hits.
InterProiIPR003109. GoLoco_motif.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PfamiPF02188. GoLoco. 4 hits.
PF13176. TPR_7. 2 hits.
PF13181. TPR_8. 1 hit.
[Graphical view]
SMARTiSM00390. GoLoco. 4 hits.
SM00028. TPR. 7 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 2 hits.
PROSITEiPS50877. GOLOCO. 4 hits.
PS50005. TPR. 6 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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. Translation: CAI14361.1.
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.
GeneIDi29899.
KEGGihsa:29899.
UCSCiuc010ovc.3. human.

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. Translation: CAI14361.1.
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. 13 interactors.
DIPiDIP-399N.
IntActiP81274. 16 interactors.
MINTiMINT-3023522.
STRINGi9606.ENSP00000264126.

PTM databases

iPTMnetiP81274.
PhosphoSitePlusiP81274.

Polymorphism and mutation databases

BioMutaiGPSM2.
DMDMi294862507.

Proteomic databases

EPDiP81274.
MaxQBiP81274.
PaxDbiP81274.
PeptideAtlasiP81274.
PRIDEiP81274.

Protocols and materials databases

DNASUi29899.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi29899.
DisGeNETi29899.
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.
OMAiIMRSQAK.
OrthoDBiEOG091G04C9.
PhylomeDBiP81274.
TreeFamiTF328344.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000121957-MONOMER.
SIGNORiP81274.

Miscellaneous databases

GeneWikiiGPSM2.
GenomeRNAii29899.
PROiP81274.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121957.
CleanExiHS_GPSM2.
ExpressionAtlasiP81274. baseline and differential.
GenevisibleiP81274. HS.

Family and domain databases

Gene3Di1.25.40.10. 2 hits.
InterProiIPR003109. GoLoco_motif.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PfamiPF02188. GoLoco. 4 hits.
PF13176. TPR_7. 2 hits.
PF13181. TPR_8. 1 hit.
[Graphical view]
SMARTiSM00390. GoLoco. 4 hits.
SM00028. TPR. 7 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 2 hits.
PROSITEiPS50877. GOLOCO. 4 hits.
PS50005. TPR. 6 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGPSM2_HUMAN
AccessioniPrimary (citable) accession number: P81274
Secondary accession number(s): Q5T1N8, Q6IBL7, Q8N0Z5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: April 20, 2010
Last modified: November 30, 2016
This is version 173 of the entry and version 3 of the sequence. [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

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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.