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Protein

Repulsive guidance molecule A

Gene

RGMA

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

Functioni

Member of the repulsive guidance molecule (RGM) family that performs several functions in the developing and adult nervous system. Regulates cephalic neural tube closure, inhibits neurite outgrowth and cortical neuron branching, and the formation of mature synapses. Binding to its receptor NEO1/neogenin induces activation of RHOA-ROCK1/Rho-kinase signaling pathway through UNC5B-ARHGEF12/LARG-PTK2/FAK1 cascade, leading to collapse of the neuronal growth cone and neurite outgrowth inhibition. Furthermore, RGMA binding to NEO1/neogenin leads to HRAS inactivation by influencing HRAS-PTK2/FAK1-AKT1 pathway. It also functions as a bone morphogenetic protein (BMP) coreceptor that may signal through SMAD1, SMAD5, and SMAD8.2 Publications

GO - Molecular functioni

  • coreceptor activity Source: GO_Central
  • glycoprotein binding Source: BHF-UCL
  • transferrin receptor binding Source: BHF-UCL

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

BioCyciZFISH:G66-32716-MONOMER.
ReactomeiR-HSA-373752. Netrin-1 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Repulsive guidance molecule A
Alternative name(s):
RGM domain family member A
Gene namesi
Name:RGMA
Synonyms:RGM
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:30308. RGMA.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi56963.
PharmGKBiPA128394693.

Polymorphism and mutation databases

BioMutaiRGMA.
DMDMi296452979.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 47Sequence analysisAdd BLAST47
PropeptideiPRO_000003038548 – 168Removed in mature formBy similarityAdd BLAST121
ChainiPRO_0000030386169 – 424Repulsive guidance molecule AAdd BLAST256
PropeptideiPRO_0000030387425 – 450Removed in mature formSequence analysisAdd BLAST26

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi114N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi145 ↔ 226By similarity
Glycosylationi159N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi163 ↔ 315By similarity
Glycosylationi389N-linked (GlcNAc...)Sequence analysis1
Lipidationi424GPI-anchor amidated alanineSequence analysis1

Post-translational modificationi

Autocatalytically cleaved at low pH; the two chains remain linked via two disulfide bonds.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei168 – 169Cleavage; by autolysisBy similarity2

Keywords - PTMi

Autocatalytic cleavage, Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PaxDbiQ96B86.
PeptideAtlasiQ96B86.
PRIDEiQ96B86.

PTM databases

iPTMnetiQ96B86.
PhosphoSitePlusiQ96B86.

Expressioni

Gene expression databases

BgeeiENSG00000182175.
CleanExiHS_RGMA.
ExpressionAtlasiQ96B86. baseline and differential.
GenevisibleiQ96B86. HS.

Organism-specific databases

HPAiCAB012343.
HPA039880.
HPA044222.

Interactioni

Subunit structurei

Interacts with NEO1, BMP2 and BMP4.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
TERF2IPQ9NYB02EBI-722102,EBI-750109

GO - Molecular functioni

  • transferrin receptor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi121284. 14 interactors.
DIPiDIP-61606N.
IntActiQ96B86. 14 interactors.
MINTiMINT-1420050.
STRINGi9606.ENSP00000452126.

Structurei

Secondary structure

1450
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi50 – 60Combined sources11
Helixi77 – 89Combined sources13
Helixi90 – 92Combined sources3
Helixi97 – 112Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4UHYX-ray3.20C46-139[»]
ProteinModelPortaliQ96B86.
SMRiQ96B86.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IFAH. Eukaryota.
ENOG410ZT7E. LUCA.
HOGENOMiHOG000013072.
HOVERGENiHBG057627.
InParanoidiQ96B86.
KOiK06847.
PhylomeDBiQ96B86.
TreeFamiTF329836.

Family and domain databases

InterProiIPR009496. RGM_C.
IPR010536. RGM_N.
IPR033607. RGMA.
[Graphical view]
PANTHERiPTHR31428:SF4. PTHR31428:SF4. 1 hit.
PfamiPF06534. RGM_C. 1 hit.
PF06535. RGM_N. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q96B86-1) [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
MQPPRERLVV TGRAGWMGMG RGAGRSALGF WPTLAFLLCS FPAATSPCKI
60 70 80 90 100
LKCNSEFWSA TSGSHAPASD DTPEFCAALR SYALCTRRTA RTCRGDLAYH
110 120 130 140 150
SAVHGIEDLM SQHNCSKDGP TSQPRLRTLP PAGDSQERSD SPEICHYEKS
160 170 180 190 200
FHKHSATPNY THCGLFGDPH LRTFTDRFQT CKVQGAWPLI DNNYLNVQVT
210 220 230 240 250
NTPVLPGSAA TATSKLTIIF KNFQECVDQK VYQAEMDELP AAFVDGSKNG
260 270 280 290 300
GDKHGANSLK ITEKVSGQHV EIQAKYIGTT IVVRQVGRYL TFAVRMPEEV
310 320 330 340 350
VNAVEDWDSQ GLYLCLRGCP LNQQIDFQAF HTNAEGTGAR RLAAASPAPT
360 370 380 390 400
APETFPYETA VAKCKEKLPV EDLYYQACVF DLLTTGDVNF TLAAYYALED
410 420 430 440 450
VKMLHSNKDK LHLYDRTRDL PGRAAAGLPL APRPLLGALV PLLALLPVFC
Length:450
Mass (Da):49,347
Last modified:May 18, 2010 - v3
Checksum:iE3244FA43A029DCF
GO
Isoform 2 (identifier: Q96B86-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-16: Missing.

Show »
Length:434
Mass (Da):47,512
Checksum:i219D630DAEF61745
GO
Isoform 3 (identifier: Q96B86-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-4: MQPP → MGGLGPRRAGTS

Note: No experimental confirmation available.
Show »
Length:458
Mass (Da):50,035
Checksum:iE01D353C68437163
GO

Sequence cautioni

The sequence AAH15886 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAB98207 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti199V → A in BAC11285 (PubMed:14702039).Curated1
Sequence conflicti314L → P in BAH13014 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_062144415D → E.5 PublicationsCorresponds to variant rs4238485dbSNPEnsembl.1
Natural variantiVAR_060105431A → V.Corresponds to variant rs4778078dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0540701 – 16Missing in isoform 2. 3 PublicationsAdd BLAST16
Alternative sequenceiVSP_0540711 – 4MQPP → MGGLGPRRAGTS in isoform 3. 1 Publication4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL390083 mRNA. Translation: CAB98207.1. Different initiation.
AL136826 mRNA. Translation: CAB66760.1.
AK074910 mRNA. Translation: BAC11285.1.
AK074966 mRNA. Translation: BAC11321.1.
AK074980 mRNA. Translation: BAC11330.1.
AK299363 mRNA. Translation: BAH13014.1.
AC087641 Genomic DNA. No translation available.
CH471101 Genomic DNA. Translation: EAX02167.1.
BC015886 mRNA. Translation: AAH15886.2. Different initiation.
BC140838 mRNA. Translation: AAI40839.1.
BC151132 mRNA. Translation: AAI51133.1.
CCDSiCCDS45357.1. [Q96B86-1]
CCDS53973.1. [Q96B86-3]
CCDS53974.1. [Q96B86-4]
RefSeqiNP_001159755.1. NM_001166283.1.
NP_001159758.1. NM_001166286.1.
NP_001159759.1. NM_001166287.1.
NP_001159760.1. NM_001166288.1.
NP_001159761.1. NM_001166289.1.
NP_064596.2. NM_020211.2.
UniGeneiHs.271277.

Genome annotation databases

EnsembliENST00000329082; ENSP00000330005; ENSG00000182175.
ENST00000425933; ENSP00000404442; ENSG00000182175.
ENST00000542321; ENSP00000440025; ENSG00000182175.
ENST00000543599; ENSP00000442498; ENSG00000182175.
GeneIDi56963.
KEGGihsa:56963.
UCSCiuc002bsq.3. human. [Q96B86-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL390083 mRNA. Translation: CAB98207.1. Different initiation.
AL136826 mRNA. Translation: CAB66760.1.
AK074910 mRNA. Translation: BAC11285.1.
AK074966 mRNA. Translation: BAC11321.1.
AK074980 mRNA. Translation: BAC11330.1.
AK299363 mRNA. Translation: BAH13014.1.
AC087641 Genomic DNA. No translation available.
CH471101 Genomic DNA. Translation: EAX02167.1.
BC015886 mRNA. Translation: AAH15886.2. Different initiation.
BC140838 mRNA. Translation: AAI40839.1.
BC151132 mRNA. Translation: AAI51133.1.
CCDSiCCDS45357.1. [Q96B86-1]
CCDS53973.1. [Q96B86-3]
CCDS53974.1. [Q96B86-4]
RefSeqiNP_001159755.1. NM_001166283.1.
NP_001159758.1. NM_001166286.1.
NP_001159759.1. NM_001166287.1.
NP_001159760.1. NM_001166288.1.
NP_001159761.1. NM_001166289.1.
NP_064596.2. NM_020211.2.
UniGeneiHs.271277.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4UHYX-ray3.20C46-139[»]
ProteinModelPortaliQ96B86.
SMRiQ96B86.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121284. 14 interactors.
DIPiDIP-61606N.
IntActiQ96B86. 14 interactors.
MINTiMINT-1420050.
STRINGi9606.ENSP00000452126.

PTM databases

iPTMnetiQ96B86.
PhosphoSitePlusiQ96B86.

Polymorphism and mutation databases

BioMutaiRGMA.
DMDMi296452979.

Proteomic databases

PaxDbiQ96B86.
PeptideAtlasiQ96B86.
PRIDEiQ96B86.

Protocols and materials databases

DNASUi56963.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000329082; ENSP00000330005; ENSG00000182175.
ENST00000425933; ENSP00000404442; ENSG00000182175.
ENST00000542321; ENSP00000440025; ENSG00000182175.
ENST00000543599; ENSP00000442498; ENSG00000182175.
GeneIDi56963.
KEGGihsa:56963.
UCSCiuc002bsq.3. human. [Q96B86-1]

Organism-specific databases

CTDi56963.
DisGeNETi56963.
GeneCardsiRGMA.
HGNCiHGNC:30308. RGMA.
HPAiCAB012343.
HPA039880.
HPA044222.
MIMi607362. gene.
neXtProtiNX_Q96B86.
PharmGKBiPA128394693.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFAH. Eukaryota.
ENOG410ZT7E. LUCA.
HOGENOMiHOG000013072.
HOVERGENiHBG057627.
InParanoidiQ96B86.
KOiK06847.
PhylomeDBiQ96B86.
TreeFamiTF329836.

Enzyme and pathway databases

BioCyciZFISH:G66-32716-MONOMER.
ReactomeiR-HSA-373752. Netrin-1 signaling.

Miscellaneous databases

ChiTaRSiRGMA. human.
GeneWikiiRGMA.
GenomeRNAii56963.
PROiQ96B86.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000182175.
CleanExiHS_RGMA.
ExpressionAtlasiQ96B86. baseline and differential.
GenevisibleiQ96B86. HS.

Family and domain databases

InterProiIPR009496. RGM_C.
IPR010536. RGM_N.
IPR033607. RGMA.
[Graphical view]
PANTHERiPTHR31428:SF4. PTHR31428:SF4. 1 hit.
PfamiPF06534. RGM_C. 1 hit.
PF06535. RGM_N. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRGMA_HUMAN
AccessioniPrimary (citable) accession number: Q96B86
Secondary accession number(s): B2RTW1
, B7Z5S8, F5GXQ7, F5GZU6, G3V518, Q0JV97, Q8NC80, Q9H0E6, Q9NPM3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: May 18, 2010
Last modified: November 2, 2016
This is version 115 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: 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
  6. 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.