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Q96B86

- RGMA_HUMAN

UniProt

Q96B86 - RGMA_HUMAN

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Protein

Repulsive guidance molecule A

Gene

RGMA

Organism
Homo sapiens (Human)
Status
Reviewed - 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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei168 – 1692Cleavage; by autolysisBy similarity

GO - Molecular functioni

  1. coreceptor activity Source: Ensembl

GO - Biological processi

  1. axon guidance Source: Reactome
  2. BMP signaling pathway Source: Ensembl
  3. neural tube closure Source: Ensembl
  4. regulation of BMP signaling pathway Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_22237. 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
ProteomesiUP000005640: Chromosome 15

Organism-specific databases

HGNCiHGNC:30308. RGMA.

Subcellular locationi

Cell membrane By similarity; Lipid-anchorGPI-anchor By similarity

GO - Cellular componenti

  1. anchored component of membrane Source: UniProtKB-KW
  2. cell surface Source: Ensembl
  3. endoplasmic reticulum Source: LIFEdb
  4. extracellular vesicular exosome Source: UniProt
  5. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA128394693.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 4747Sequence AnalysisAdd
BLAST
Propeptidei48 – 168121Removed in mature formBy similarityPRO_0000030385Add
BLAST
Chaini169 – 424256Repulsive guidance molecule APRO_0000030386Add
BLAST
Propeptidei425 – 45026Removed in mature formSequence AnalysisPRO_0000030387Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi114 – 1141N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi145 ↔ 226By similarity
Glycosylationi159 – 1591N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi163 ↔ 315By similarity
Glycosylationi389 – 3891N-linked (GlcNAc...)Sequence Analysis
Lipidationi424 – 4241GPI-anchor amidated alanineSequence Analysis

Post-translational modificationi

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

Keywords - PTMi

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

Proteomic databases

PaxDbiQ96B86.
PRIDEiQ96B86.

PTM databases

PhosphoSiteiQ96B86.

Expressioni

Gene expression databases

BgeeiQ96B86.
CleanExiHS_RGMA.
ExpressionAtlasiQ96B86. baseline and differential.
GenevestigatoriQ96B86.

Organism-specific databases

HPAiCAB012343.

Interactioni

Subunit structurei

Interacts with NEO1, BMP2 and BMP4.By similarity

Protein-protein interaction databases

BioGridi121284. 3 interactions.
IntActiQ96B86. 2 interactions.
MINTiMINT-1420050.
STRINGi9606.ENSP00000330005.

Structurei

3D structure databases

ProteinModelPortaliQ96B86.
SMRiQ96B86. Positions 169-326.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG87951.
GeneTreeiENSGT00390000008488.
HOGENOMiHOG000013072.
HOVERGENiHBG057627.
InParanoidiQ96B86.
KOiK06847.
OMAiPLNQQID.
OrthoDBiEOG7VQJDC.
PhylomeDBiQ96B86.
TreeFamiTF329836.

Family and domain databases

InterProiIPR009496. RGM_C.
IPR010536. RGM_N.
[Graphical view]
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. Align

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 AAH15886.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.
The sequence CAB98207.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti199 – 1991V → A in BAC11285. (PubMed:14702039)Curated
Sequence conflicti314 – 3141L → P in BAH13014. (PubMed:14702039)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti415 – 4151D → E.5 Publications
Corresponds to variant rs4238485 [ dbSNP | Ensembl ].
VAR_062144
Natural varianti431 – 4311A → V.
Corresponds to variant rs4778078 [ dbSNP | Ensembl ].
VAR_060105

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1616Missing in isoform 2. 3 PublicationsVSP_054070Add
BLAST
Alternative sequencei1 – 44MQPP → MGGLGPRRAGTS in isoform 3. 1 PublicationVSP_054071

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.2. human. [Q96B86-1]

Polymorphism databases

DMDMi296452979.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS45357.1. [Q96B86-1 ]
CCDS53973.1. [Q96B86-3 ]
CCDS53974.1. [Q96B86-4 ]
RefSeqi NP_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.
UniGenei Hs.271277.

3D structure databases

ProteinModelPortali Q96B86.
SMRi Q96B86. Positions 169-326.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 121284. 3 interactions.
IntActi Q96B86. 2 interactions.
MINTi MINT-1420050.
STRINGi 9606.ENSP00000330005.

PTM databases

PhosphoSitei Q96B86.

Polymorphism databases

DMDMi 296452979.

Proteomic databases

PaxDbi Q96B86.
PRIDEi Q96B86.

Protocols and materials databases

DNASUi 56963.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000329082 ; ENSP00000330005 ; ENSG00000182175 .
ENST00000425933 ; ENSP00000404442 ; ENSG00000182175 .
ENST00000542321 ; ENSP00000440025 ; ENSG00000182175 .
ENST00000543599 ; ENSP00000442498 ; ENSG00000182175 .
GeneIDi 56963.
KEGGi hsa:56963.
UCSCi uc002bsq.2. human. [Q96B86-1 ]

Organism-specific databases

CTDi 56963.
GeneCardsi GC15M093586.
HGNCi HGNC:30308. RGMA.
HPAi CAB012343.
MIMi 607362. gene.
neXtProti NX_Q96B86.
PharmGKBi PA128394693.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG87951.
GeneTreei ENSGT00390000008488.
HOGENOMi HOG000013072.
HOVERGENi HBG057627.
InParanoidi Q96B86.
KOi K06847.
OMAi PLNQQID.
OrthoDBi EOG7VQJDC.
PhylomeDBi Q96B86.
TreeFami TF329836.

Enzyme and pathway databases

Reactomei REACT_22237. Netrin-1 signaling.

Miscellaneous databases

ChiTaRSi RGMA. human.
GeneWikii RGMA.
GenomeRNAii 56963.
NextBioi 62595.
PROi Q96B86.
SOURCEi Search...

Gene expression databases

Bgeei Q96B86.
CleanExi HS_RGMA.
ExpressionAtlasi Q96B86. baseline and differential.
Genevestigatori Q96B86.

Family and domain databases

InterProi IPR009496. RGM_C.
IPR010536. RGM_N.
[Graphical view ]
Pfami PF06534. RGM_C. 1 hit.
PF06535. RGM_N. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. The European IMAGE consortium
    Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT GLU-415.
    Tissue: Retina.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLU-415.
    Tissue: Testis.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT GLU-415.
    Tissue: Teratocarcinoma.
  4. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
    , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLU-415.
  6. "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), VARIANT GLU-415.
    Tissue: Brain and Uterus.
  7. "Unc5B associates with LARG to mediate the action of repulsive guidance molecule."
    Hata K., Kaibuchi K., Inagaki S., Yamashita T.
    J. Cell Biol. 184:737-750(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Inactivation of Ras by p120GAP via focal adhesion kinase dephosphorylation mediates RGMa-induced growth cone collapse."
    Endo M., Yamashita T.
    J. Neurosci. 29:6649-6662(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

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: October 29, 2014
This is version 94 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

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. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3