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Protein

Germinal center-associated signaling and motility protein

Gene

GCSAM

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

Functioni

Involved in the negative regulation of lymphocyte motility. It mediates the migration-inhibitory effects of IL6. Serves as a positive regulator of the RhoA signaling pathway. Enhancement of RhoA activation results in inhibition of lymphocyte and lymphoma cell motility by activation of its downstream effector ROCK. Is a regulator of B-cell receptor signaling, that acts through SYK kinase activation.3 Publications

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • myosin II binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

GO - Biological processi

  • negative regulation of lymphocyte migration Source: UniProtKB
  • regulation of B cell receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Germinal center-associated signaling and motility protein
Alternative name(s):
Germinal center B-cell-expressed transcript 2 protein
Germinal center-associated lymphoma protein
Short name:
hGAL
Gene namesi
Name:GCSAM
Synonyms:GAL, GCET2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:20253. GCSAM.

Subcellular locationi

  • Cytoplasm
  • Cell membrane

  • Note: It relocalizes from the cytoplasm to podosome-like structures upon cell treatment with IL6.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi106 – 1072YY → AA: Does not affect the interaction with SYK. 1 Publication
Mutagenesisi128 – 1281Y → F: Does not affect IL6 induced phosphorylation. Does not affect the interaction with SYK. 2 Publications
Mutagenesisi148 – 1481Y → F: Prevents IL6 induced phosphorylation. Does not affect the interaction with SYK. 2 Publications

Organism-specific databases

PharmGKBiPA134980592.

Polymorphism and mutation databases

BioMutaiGCSAM.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 178178Germinal center-associated signaling and motility proteinPRO_0000256228Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei99 – 991PhosphoserineBy similarity
Modified residuei148 – 1481PhosphotyrosineCombined sources

Post-translational modificationi

Phosphorylation on tyrosine residues can be induced by IL6. Phosphorylation is mediated by LYN.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8N6F7.
PaxDbiQ8N6F7.
PeptideAtlasiQ8N6F7.
PRIDEiQ8N6F7.

PTM databases

iPTMnetiQ8N6F7.
PhosphoSiteiQ8N6F7.
SwissPalmiQ8N6F7.

Expressioni

Tissue specificityi

Expressed in diffuse large B-cell lymphoma (DLBCL) and several germinal center (GC)-like lymphoma cell lines (at protein level). Highly expressed in normal GC lymphocytes and GC-derived malignancies. Expressed in thymus and spleen.3 Publications

Inductioni

Up-regulated by IL4/interleukin-4.1 Publication

Gene expression databases

BgeeiQ8N6F7.
CleanExiHS_GAL.
HS_GCET2.
ExpressionAtlasiQ8N6F7. baseline and differential.
GenevisibleiQ8N6F7. HS.

Organism-specific databases

HPAiHPA002473.

Interactioni

Subunit structurei

Interacts with ACTB and MYH2; the interaction with MYH2 is increased by IL6-induced phosphorylation. Interacts (via C-terminus) with ARHGEF11 (via DH domain). Interacts with ARHGEF12. Interacts with SYK; the interaction increases after B-cell receptor stimulation, resulting in enhanced SYK autophosphorylation and activity.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
APPBP2Q926243EBI-10267082,EBI-743771

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • myosin II binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi129200. 1 interaction.
IntActiQ8N6F7. 1 interaction.
STRINGi9606.ENSP00000419485.

Structurei

3D structure databases

ProteinModelPortaliQ8N6F7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Phylogenomic databases

eggNOGiENOG410JBYS. Eukaryota.
ENOG41115IK. LUCA.
GeneTreeiENSGT00730000111441.
HOGENOMiHOG000293224.
HOVERGENiHBG081549.
InParanoidiQ8N6F7.
OMAiEGCFCLP.
OrthoDBiEOG78M03C.
PhylomeDBiQ8N6F7.
TreeFamiTF338596.

Family and domain databases

InterProiIPR031364. GC_assoc_lym.
[Graphical view]
PfamiPF15666. HGAL. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N6F7-1) [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
MGNSLLRENR RQQNTQEMPW NVRMQSPKQR TSRCWDHHIA EGCFCLPWKK
60 70 80 90 100
ILIFEKRQDS QNENERMSST PIQDNVDQTY SEELCYTLIN HRVLCTRPSG
110 120 130 140 150
NSAEEYYENV PCKAERPRES LGGTETEYSL LHMPSTDPRH ARSPEDEYEL
160 170
LMPHRISSHF LQQPRPLMAP SETQFSHL
Length:178
Mass (Da):21,005
Last modified:October 1, 2002 - v1
Checksum:iB7C91F3D4B78CD03
GO
Isoform 2 (identifier: Q8N6F7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     9-9: N → NSF

Note: No experimental confirmation available.
Show »
Length:180
Mass (Da):21,240
Checksum:iF28DC1F48452F889
GO
Isoform 3 (identifier: Q8N6F7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     34-48: Missing.

Note: Gene prediction based on EST data.
Show »
Length:163
Mass (Da):19,206
Checksum:i482C190FAF5BFCA5
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei9 – 91N → NSF in isoform 2. 1 PublicationVSP_046085
Alternative sequencei34 – 4815Missing in isoform 3. CuratedVSP_046984Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY212246 mRNA. Translation: AAO22147.1.
AF521911 mRNA. Translation: AAO21701.1.
AC128688 Genomic DNA. No translation available.
BC030506 mRNA. Translation: AAH30506.1.
BM456595 mRNA. No translation available.
CCDSiCCDS2964.1. [Q8N6F7-1]
CCDS54621.1. [Q8N6F7-3]
CCDS54622.1. [Q8N6F7-2]
RefSeqiNP_001177188.1. NM_001190259.1. [Q8N6F7-2]
NP_001177189.1. NM_001190260.1. [Q8N6F7-3]
NP_689998.1. NM_152785.4. [Q8N6F7-1]
UniGeneiHs.49614.

Genome annotation databases

EnsembliENST00000308910; ENSP00000309487; ENSG00000174500. [Q8N6F7-1]
ENST00000460387; ENSP00000420603; ENSG00000174500. [Q8N6F7-3]
ENST00000484193; ENSP00000419485; ENSG00000174500. [Q8N6F7-2]
GeneIDi257144.
KEGGihsa:257144.
UCSCiuc003dys.2. human. [Q8N6F7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY212246 mRNA. Translation: AAO22147.1.
AF521911 mRNA. Translation: AAO21701.1.
AC128688 Genomic DNA. No translation available.
BC030506 mRNA. Translation: AAH30506.1.
BM456595 mRNA. No translation available.
CCDSiCCDS2964.1. [Q8N6F7-1]
CCDS54621.1. [Q8N6F7-3]
CCDS54622.1. [Q8N6F7-2]
RefSeqiNP_001177188.1. NM_001190259.1. [Q8N6F7-2]
NP_001177189.1. NM_001190260.1. [Q8N6F7-3]
NP_689998.1. NM_152785.4. [Q8N6F7-1]
UniGeneiHs.49614.

3D structure databases

ProteinModelPortaliQ8N6F7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi129200. 1 interaction.
IntActiQ8N6F7. 1 interaction.
STRINGi9606.ENSP00000419485.

PTM databases

iPTMnetiQ8N6F7.
PhosphoSiteiQ8N6F7.
SwissPalmiQ8N6F7.

Polymorphism and mutation databases

BioMutaiGCSAM.

Proteomic databases

MaxQBiQ8N6F7.
PaxDbiQ8N6F7.
PeptideAtlasiQ8N6F7.
PRIDEiQ8N6F7.

Protocols and materials databases

DNASUi257144.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000308910; ENSP00000309487; ENSG00000174500. [Q8N6F7-1]
ENST00000460387; ENSP00000420603; ENSG00000174500. [Q8N6F7-3]
ENST00000484193; ENSP00000419485; ENSG00000174500. [Q8N6F7-2]
GeneIDi257144.
KEGGihsa:257144.
UCSCiuc003dys.2. human. [Q8N6F7-1]

Organism-specific databases

CTDi257144.
GeneCardsiGCSAM.
HGNCiHGNC:20253. GCSAM.
HPAiHPA002473.
MIMi607792. gene.
neXtProtiNX_Q8N6F7.
PharmGKBiPA134980592.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JBYS. Eukaryota.
ENOG41115IK. LUCA.
GeneTreeiENSGT00730000111441.
HOGENOMiHOG000293224.
HOVERGENiHBG081549.
InParanoidiQ8N6F7.
OMAiEGCFCLP.
OrthoDBiEOG78M03C.
PhylomeDBiQ8N6F7.
TreeFamiTF338596.

Miscellaneous databases

GenomeRNAii257144.
PROiQ8N6F7.
SOURCEiSearch...

Gene expression databases

BgeeiQ8N6F7.
CleanExiHS_GAL.
HS_GCET2.
ExpressionAtlasiQ8N6F7. baseline and differential.
GenevisibleiQ8N6F7. HS.

Family and domain databases

InterProiIPR031364. GC_assoc_lym.
[Graphical view]
PfamiPF15666. HGAL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Two newly characterized germinal center B-cell-associated genes, GCET1 and GCET2, have differential expression in normal and neoplastic B cells."
    Pan Z., Shen Y., Du C., Zhou G., Rosenwald A., Staudt L.M., Greiner T.C., McKeithan T.W., Chan W.C.
    Am. J. Pathol. 163:135-144(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
  2. "HGAL is a novel interleukin-4-inducible gene that strongly predicts survival in diffuse large B-cell lymphoma."
    Lossos I.S., Alizadeh A.A., Rajapaksa R., Tibshirani R., Levy R.
    Blood 101:433-440(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, TISSUE SPECIFICITY.
  3. "The DNA sequence, annotation and analysis of human chromosome 3."
    Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J.
    , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
    Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Lymphoma.
  5. "Expression of the human germinal center-associated lymphoma (HGAL) protein, a new marker of germinal center B-cell derivation."
    Natkunam Y., Lossos I.S., Taidi B., Zhao S., Lu X., Ding F., Hammer A.S., Marafioti T., Byrne G.E. Jr., Levy S., Warnke R.A., Levy R.
    Blood 105:3979-3986(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  6. "HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and mediates the effects of IL-6 on cell migration."
    Lu X., Chen J., Malumbres R., Cubedo Gil E., Helfman D.M., Lossos I.S.
    Blood 110:4268-4277(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MYH2 AND ACTB, PHOSPHORYLATION BY LYN, MUTAGENESIS OF TYR-128 AND TYR-148.
  7. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-148, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  8. "HGAL, a germinal center specific protein, decreases lymphoma cell motility by modulation of the RhoA signaling pathway."
    Jiang X., Lu X., McNamara G., Liu X., Cubedo E., Sarosiek K.A., Sanchez-Garcia I., Helfman D.M., Lossos I.S.
    Blood 116:5217-5227(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ARHGEF11 AND ARHGEF12.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. Cited for: FUNCTION AS REGULATOR OF B-CELL RECEPTOR SIGNALING, INTERACTION WITH SYK, SUBCELLULAR LOCATION, MUTAGENESIS OF 106-TYR-TYR-107; TYR-128 AND TYR-148.

Entry informationi

Entry nameiGCSAM_HUMAN
AccessioniPrimary (citable) accession number: Q8N6F7
Secondary accession number(s): C9JD17, C9JUG6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 31, 2006
Last sequence update: October 1, 2002
Last modified: July 6, 2016
This is version 101 of the entry and version 1 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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.