GCSAM_HUMAN
ID GCSAM_HUMAN Reviewed; 178 AA.
AC Q8N6F7; C9JD17; C9JUG6;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Germinal center-associated signaling and motility protein;
DE AltName: Full=Germinal center B-cell-expressed transcript 2 protein;
DE AltName: Full=Germinal center-associated lymphoma protein;
DE Short=hGAL;
GN Name=GCSAM; Synonyms=GAL, GCET2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=12819018; DOI=10.1016/s0002-9440(10)63637-1;
RA Pan Z., Shen Y., Du C., Zhou G., Rosenwald A., Staudt L.M., Greiner T.C.,
RA McKeithan T.W., Chan W.C.;
RT "Two newly characterized germinal center B-cell-associated genes, GCET1 and
RT GCET2, have differential expression in normal and neoplastic B cells.";
RL Am. J. Pathol. 163:135-144(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=12509382; DOI=10.1182/blood-2002-06-1931;
RA Lossos I.S., Alizadeh A.A., Rajapaksa R., Tibshirani R., Levy R.;
RT "HGAL is a novel interleukin-4-inducible gene that strongly predicts
RT survival in diffuse large B-cell lymphoma.";
RL Blood 101:433-440(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lymphoma;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=15677569; DOI=10.1182/blood-2004-08-3112;
RA Natkunam Y., Lossos I.S., Taidi B., Zhao S., Lu X., Ding F., Hammer A.S.,
RA Marafioti T., Byrne G.E. Jr., Levy S., Warnke R.A., Levy R.;
RT "Expression of the human germinal center-associated lymphoma (HGAL)
RT protein, a new marker of germinal center B-cell derivation.";
RL Blood 105:3979-3986(2005).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MYH2 AND ACTB,
RP PHOSPHORYLATION BY LYN, AND MUTAGENESIS OF TYR-128 AND TYR-148.
RX PubMed=17823310; DOI=10.1182/blood-2007-04-087775;
RA Lu X., Chen J., Malumbres R., Cubedo Gil E., Helfman D.M., Lossos I.S.;
RT "HGAL, a lymphoma prognostic biomarker, interacts with the cytoskeleton and
RT mediates the effects of IL-6 on cell migration.";
RL Blood 110:4268-4277(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-148, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ARHGEF11 AND ARHGEF12.
RX PubMed=20844236; DOI=10.1182/blood-2010-04-281568;
RA Jiang X., Lu X., McNamara G., Liu X., Cubedo E., Sarosiek K.A.,
RA Sanchez-Garcia I., Helfman D.M., Lossos I.S.;
RT "HGAL, a germinal center specific protein, decreases lymphoma cell motility
RT by modulation of the RhoA signaling pathway.";
RL Blood 116:5217-5227(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP FUNCTION AS REGULATOR OF B-CELL RECEPTOR SIGNALING, INTERACTION WITH SYK,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 106-TYR-TYR-107; TYR-128 AND
RP TYR-148.
RX PubMed=23299888; DOI=10.1038/ncomms2334;
RA Romero-Camarero I., Jiang X., Natkunam Y., Lu X., Vicente-Duenas C.,
RA Gonzalez-Herrero I., Flores T., Garcia J.L., McNamara G., Kunder C.,
RA Zhao S., Segura V., Fontan L., Martinez-Climent J.A., Garcia-Criado F.J.,
RA Theis J.D., Dogan A., Campos-Sanchez E., Green M.R., Alizadeh A.A.,
RA Cobaleda C., Sanchez-Garcia I., Lossos I.S.;
RT "Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis
RT via BCR-mediated Syk activation.";
RL Nat. Commun. 4:1338-1338(2013).
CC -!- FUNCTION: Involved in the negative regulation of lymphocyte motility.
CC It mediates the migration-inhibitory effects of IL6. Serves as a
CC positive regulator of the RhoA signaling pathway. Enhancement of RhoA
CC activation results in inhibition of lymphocyte and lymphoma cell
CC motility by activation of its downstream effector ROCK. Is a regulator
CC of B-cell receptor signaling, that acts through SYK kinase activation.
CC {ECO:0000269|PubMed:17823310, ECO:0000269|PubMed:20844236,
CC ECO:0000269|PubMed:23299888}.
CC -!- SUBUNIT: Interacts with ACTB and MYH2; the interaction with MYH2 is
CC increased by IL6-induced phosphorylation. Interacts (via C-terminus)
CC with ARHGEF11 (via DH domain). Interacts with ARHGEF12. Interacts with
CC SYK; the interaction increases after B-cell receptor stimulation,
CC resulting in enhanced SYK autophosphorylation and activity.
CC {ECO:0000269|PubMed:17823310, ECO:0000269|PubMed:20844236,
CC ECO:0000269|PubMed:23299888}.
CC -!- INTERACTION:
CC Q8N6F7; Q9BXS5: AP1M1; NbExp=3; IntAct=EBI-10267082, EBI-541426;
CC Q8N6F7; Q92624: APPBP2; NbExp=6; IntAct=EBI-10267082, EBI-743771;
CC Q8N6F7; Q9NZN8: CNOT2; NbExp=3; IntAct=EBI-10267082, EBI-743033;
CC Q8N6F7; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-10267082, EBI-3867333;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane. Note=It relocalizes
CC from the cytoplasm to podosome-like structures upon cell treatment with
CC IL6.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8N6F7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N6F7-2; Sequence=VSP_046085;
CC Name=3;
CC IsoId=Q8N6F7-3; Sequence=VSP_046984;
CC -!- TISSUE SPECIFICITY: Expressed in diffuse large B-cell lymphoma (DLBCL)
CC and several germinal center (GC)-like lymphoma cell lines (at protein
CC level). Highly expressed in normal GC lymphocytes and GC-derived
CC malignancies. Expressed in thymus and spleen.
CC {ECO:0000269|PubMed:12509382, ECO:0000269|PubMed:12819018,
CC ECO:0000269|PubMed:15677569}.
CC -!- INDUCTION: Up-regulated by IL4/interleukin-4.
CC {ECO:0000269|PubMed:12509382}.
CC -!- PTM: Phosphorylation on tyrosine residues can be induced by IL6.
CC Phosphorylation is mediated by LYN. {ECO:0000269|PubMed:17823310}.
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DR EMBL; AY212246; AAO22147.1; -; mRNA.
DR EMBL; AF521911; AAO21701.1; -; mRNA.
DR EMBL; AC128688; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC030506; AAH30506.1; -; mRNA.
DR EMBL; BM456595; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS2964.1; -. [Q8N6F7-1]
DR CCDS; CCDS54621.1; -. [Q8N6F7-3]
DR CCDS; CCDS54622.1; -. [Q8N6F7-2]
DR RefSeq; NP_001177188.1; NM_001190259.1. [Q8N6F7-2]
DR RefSeq; NP_001177189.1; NM_001190260.1. [Q8N6F7-3]
DR RefSeq; NP_689998.1; NM_152785.4. [Q8N6F7-1]
DR AlphaFoldDB; Q8N6F7; -.
DR BioGRID; 129200; 4.
DR IntAct; Q8N6F7; 5.
DR STRING; 9606.ENSP00000419485; -.
DR iPTMnet; Q8N6F7; -.
DR PhosphoSitePlus; Q8N6F7; -.
DR SwissPalm; Q8N6F7; -.
DR BioMuta; GCSAM; -.
DR MassIVE; Q8N6F7; -.
DR MaxQB; Q8N6F7; -.
DR PaxDb; Q8N6F7; -.
DR PeptideAtlas; Q8N6F7; -.
DR PRIDE; Q8N6F7; -.
DR ProteomicsDB; 11728; -.
DR ProteomicsDB; 72164; -. [Q8N6F7-1]
DR ProteomicsDB; 9668; -.
DR Antibodypedia; 1196; 180 antibodies from 30 providers.
DR DNASU; 257144; -.
DR Ensembl; ENST00000308910.9; ENSP00000309487.4; ENSG00000174500.13. [Q8N6F7-1]
DR Ensembl; ENST00000460387.6; ENSP00000420603.2; ENSG00000174500.13. [Q8N6F7-3]
DR Ensembl; ENST00000484193.5; ENSP00000419485.1; ENSG00000174500.13. [Q8N6F7-2]
DR Ensembl; ENST00000643065.1; ENSP00000493535.1; ENSG00000284925.2. [Q8N6F7-2]
DR Ensembl; ENST00000644247.1; ENSP00000494547.1; ENSG00000284925.2. [Q8N6F7-3]
DR Ensembl; ENST00000646639.2; ENSP00000496265.1; ENSG00000284925.2. [Q8N6F7-1]
DR GeneID; 257144; -.
DR KEGG; hsa:257144; -.
DR MANE-Select; ENST00000308910.9; ENSP00000309487.4; NM_152785.5; NP_689998.1.
DR UCSC; uc003dys.2; human. [Q8N6F7-1]
DR CTD; 257144; -.
DR DisGeNET; 257144; -.
DR GeneCards; GCSAM; -.
DR HGNC; HGNC:20253; GCSAM.
DR HPA; ENSG00000174500; Group enriched (lymphoid tissue, skin).
DR MIM; 607792; gene.
DR neXtProt; NX_Q8N6F7; -.
DR OpenTargets; ENSG00000174500; -.
DR PharmGKB; PA134980592; -.
DR VEuPathDB; HostDB:ENSG00000174500; -.
DR eggNOG; ENOG502TDUK; Eukaryota.
DR GeneTree; ENSGT00940000158134; -.
DR HOGENOM; CLU_126867_0_0_1; -.
DR InParanoid; Q8N6F7; -.
DR OMA; CLPWKKM; -.
DR OrthoDB; 1401343at2759; -.
DR PhylomeDB; Q8N6F7; -.
DR TreeFam; TF338596; -.
DR PathwayCommons; Q8N6F7; -.
DR SignaLink; Q8N6F7; -.
DR BioGRID-ORCS; 257144; 10 hits in 1036 CRISPR screens.
DR GenomeRNAi; 257144; -.
DR Pharos; Q8N6F7; Tbio.
DR PRO; PR:Q8N6F7; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q8N6F7; protein.
DR Bgee; ENSG00000174500; Expressed in lymph node and 87 other tissues.
DR ExpressionAtlas; Q8N6F7; baseline and differential.
DR Genevisible; Q8N6F7; HS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IPI:UniProtKB.
DR GO; GO:0045159; F:myosin II binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:2000402; P:negative regulation of lymphocyte migration; IMP:UniProtKB.
DR GO; GO:0050855; P:regulation of B cell receptor signaling pathway; IMP:UniProtKB.
DR InterPro; IPR031364; GC_assoc_lym.
DR PANTHER; PTHR35351; PTHR35351; 1.
DR Pfam; PF15666; HGAL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Membrane; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..178
FT /note="Germinal center-associated signaling and motility
FT protein"
FT /id="PRO_0000256228"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q6RFH4"
FT MOD_RES 148
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT VAR_SEQ 9
FT /note="N -> NSF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_046085"
FT VAR_SEQ 34..48
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_046984"
FT MUTAGEN 106..107
FT /note="YY->AA: Does not affect the interaction with SYK."
FT /evidence="ECO:0000269|PubMed:23299888"
FT MUTAGEN 128
FT /note="Y->F: Does not affect IL6 induced phosphorylation.
FT Does not affect the interaction with SYK."
FT /evidence="ECO:0000269|PubMed:17823310,
FT ECO:0000269|PubMed:23299888"
FT MUTAGEN 148
FT /note="Y->F: Prevents IL6 induced phosphorylation. Does not
FT affect the interaction with SYK."
FT /evidence="ECO:0000269|PubMed:17823310,
FT ECO:0000269|PubMed:23299888"
SQ SEQUENCE 178 AA; 21005 MW; B7C91F3D4B78CD03 CRC64;
MGNSLLRENR RQQNTQEMPW NVRMQSPKQR TSRCWDHHIA EGCFCLPWKK ILIFEKRQDS
QNENERMSST PIQDNVDQTY SEELCYTLIN HRVLCTRPSG NSAEEYYENV PCKAERPRES
LGGTETEYSL LHMPSTDPRH ARSPEDEYEL LMPHRISSHF LQQPRPLMAP SETQFSHL
